dna and rna

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NH, | We SN 0 I i ¥ ‏ار‎ Ae HO—P~O—} ot 0 i ‏كر‎ : adenine : 3 - adenosine i adenylic acid (AMP) ribose ممما ممم ممم ممعم ممم م ممم ممعم مم ممع عع م مم مم ع سب ۳ 

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7 

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co, a siycine ۳ Aspartate ~ yo ‘te 2 ۱ | ‏لسسع‎ 10-Fermy) THE ‏ف یج‎ 10-Forray) THE ‏اس برد اس‎ Ribose 5-phospnat. 

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Prue CO-d ۳۳۲۶ ‏روما‎ ‏و1100‎ | Glycine ۲ Z 3 Aspartate 0 amine ‏"0و ؟ وا‎ 7 gC ~— Formate Formate->C* 3 40 ae N 1H KY Glutamine amide 

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0 HOP-OCH OY OH PRPP synthetase Ky H/o 9 1 ۱ ‏بمجمجو/‎ ‎OH OH OH OH ATP ANP S-phosphoribosy pyrophosphate PRPP OH OH ribose-5-phosphiale 

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1۷0 PP, ATP ADP +P, PRP PRA GAR FGAR 1 2 3 ATP glutamine glutamate 9'VCINE—ystormyl-THE «THE \ 4 glutamine ‏بم + ممم‎ fumarate ۸۵۴+ 8 ‏مجم‎ glutamate” FGAM 8 7 6 AICAR SAICAR: CAIR as 5 ATP : ADP + 5 2 co ‏ل‎ ‏-الا1011- "لال‎ 111 aspartate > IMP ribose-5- phosphate 

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synthetase aspartate + GTP. NAD" + Hg IMP dehy nase GDP +P, . eae Geer ‏یل‎ ‎leona 7 ‏سيا‎ ‎sats ‏وه‎ ‏مسحو سب‎ = eS glutamate + ADP + PP, NH ۷ NON LoL? nbose-5-phosphate 

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۳ ¢ ۶ Ww ors AMP deaminase ۳۳ 0 ۹ rs ۳ 7 oy Soo Sy Sy ‏صلم وام يد‎ ‏سیم(‎ "۳ 7 Raa, PO eee AMP XMP GMP Ho Ho Ho Hos >| nucectdose ‏أ ماه‎ ucts ‏ههام‎ ‎Re na 9 Pie? adenosine denise deaninass “ii sire xanthosine guanesine ۳ i 7 | pa) _— patnencteonde ‏فاع‎ ‏ركام مم ده“‎ 00000006 66 ‏مامح 3550-5-03 اما مود‎ hypoxanthine =e ‏سس‎ xanthine nn guanine ‏مه‎ HO KZ) ee ‏میم‎ ۲۷۵ vanthine 9 ‏بسي‎ ‎Ho ‎1 ‎۳ ~ pS oN ۱ ۲ uric acid 

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< hove ver hove ver hove ,سم لو دا لیر تلد امه ما سا لمیر سك وود و0 جو سعب hick oP payor ری هه یج یج سوبس ‎a‏ ‏مود موی ۲ رارسا سي ‎parte‏ ° ی ۳۳ سحه طلست سر تسد تفه و اما جمی علاط ‎LEPRT‏ ‏دك ادام موس( توت ۱ #سسمطعمد سسجارت اتنا 20 0 ‎Por‏ بصم موی همه تایه دون سای( ‎Xcouhiourts‏ ‎phosphor‏ 0ك مسحي اموا نمم 

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2ATP ۲ ۹ ‏مه با رن نع زا‎ + ۵۵ “3 00 6۵ 0H glutamine | carbamoyl phosphate HOOC-CHh-CHy-CH-COOH lutamate My 

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P, H.0 Carbamoyl x * 7 ee 2 ‏وينم‎ NAD’ phosphate 00111 3 NADH+H* orotate 4 |PRPP OMP pp, HO [ HCO; eget و نو و 

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vee ‏موه‎ یه لت تا اور ‎besyukeot; kepaic‏ ۳ ] ‎Detdboirw‏ ۳ ۴و ع و0 ‎ride wxmcophoophde spoken, OOO; dev rded OOP eoarbon kare or potter ‏هه ‎vreothtar‏ ,وی مرو موی با ‎nneverbnoopkee, & dP‏ ‎frowawkner, ‏ی وق‎ oe Baceton detay deuentodtiza oP ‏مداه‎ ark to Orbe wtb ‎Orote corheta, Type 1 ‎] he» OTO ‏سل ‎hewrtchote coca)‏ ] ‏تخب همق ‏معلا صاصه لحصكها يمحل 

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ucleobase HOBO R-o-cH, OL OH OH as 8 ‏بو بو‎ | “thioredoxin Ahloredoxin | glutaredoxin 5 57 1 thioredoxin reductase olutaredonin reductase ۴۸۵: FAD 2GSH Gssc glutathione reductase NADP* NADPH+H' ۴ NADPH + H” 

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3° END 

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0 ۱0 ADENINE 4 TO DIRECTION 

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DNA Structure Three models of DNA structure. The first shows the base pairs of DNA. The second shows the base pairs connected by the sugar/phosphate backbone. The third represents the double helix with the bases represented in blue and the sugar/phosphate backbone inred, yellow, black and white. سم 8۹9-0 ‎quanine and cytosine‏ oon thymine and adenine 

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لاع 26625 5-0 = ی وم سح ‎Backbone‏ ‎as‏ | ت۳۳ ‎Sugar‏ ee ~~ 3'-end — 5-20 عنوط 8256 

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RNA DNA 

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Cytosine-Gesunine Dave ‏تست‎ ۳ (use puiriacy 

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2 0۱۸ LEFT 6-0: -51.3 4 6 6-۵: 9 1 120 6-06: 352 + 2 0-6: 4.13 + 8 88+ 7 44+28 34 21 8 0۱۸ RIGHT 35.9 4.3 27.7 to 42.0 10.0 3.36 + 42 2.0246 1.7248 1.0255 A DNA RIGHT 33.19 16.1 to 44.1 10.9 292+ 39 130 2 9 154 * 2 5.9247 HANDEDNESS, HELICAL TWIST (DEGREES) MEAN AND STANDARD DEVIATION OBSERVED RANGE BASE PAIRS PER TURN HELIX RISE PER BASE PAIR (ANGSTROM UNITS) BASE INCLINATION (DEGREES) PROPELLER TWIST (DEGREES) BASE ROLL (DEGREES) 

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Minor groove 

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org/AB/GG/ chromosome. htmt Chromosome 

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H1 histone Nucleosome Core of 8 Histone Molecules Nucleosome http://www.accessexcellence.com/AB/GG/nucleosome.gif 

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Acetyltransferases Methyltransferases 

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2 molecules each of Linker DNA —-H2A, H2B, H3, and H4 Histone 1 Core DNA Linker DNA 

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Core of eight histone molecules / Histone H1 

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Nucleosome fiber forms left-handed helix with 6 nucleosomes per tum |) 48 11 ۳ (110A 

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FIGURE 4.8, Schemes of the A and B forms of DNA. 

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Eukaroyotic Replication Cycle (Times are for Cells Growing in Culture) 6-8 hours NA=2n -> 4n GO: Resting Phase G1: Growth & Metabolism S: DNA Replication G2: Growth of Structural Elements. Mitosis. 

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2 0 ما۲ | ‎poss‏ لین اون ‎Groat‏ ‎Prow Bo‏ ۸ هس ها ‎Crowessios Povtors‏ ‎Crowk Pastors‏ ‎POGE, TEP‏ ‎By wt wide‏ تصش ‎۳06 - ‏بصوح وم‎ VOC- tabkibtory or staukiory > depeuday oo cell ype ‎ ‎Cel Overs Ook (COC) proeke (>SO) 

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Paces OP Oitosts Balery سس وا شمسا وا پیت ۳ ‎a‏ 000 میم و 

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©. The propertes oP kaows @. oot DOO powerwes we: x. O08 polwerwe 1 ty a sknie pepe ewoded by pokD ud wed Por OOO repicatcs. Replicdes DOO tc he S'S! drevion. Wo S'S" ‏وم مور‎ wily to rewove sulevides Prow GS! ocd of OO or Pow wa ROO priver. b. ODO pobwersee 1 3 siade pepide raoded by pot. Oved Por OOO repur. :. )00( ‏مجاهم‎ 111 kes three polpeptde subvats tt he vatdyic core OP the easyer: 1 ‏اا‎ by be i? em), ‏ات‎ Randy ‏ري ا‎ be ‏هام3 ارام او نو له‎ )0 ‎drevivs.‏ 929 عا و ‎ad 006 ‏مان‎ 10 te wcernted by her chiP cece, card werd os DOOD repur. ‎e. OOO pobwersee O < ‏له ,00 برط له‎ tf» wed tc DOD repur. ‎5 ۶ 009 ‏وس سس سا‎ 999 revkrcas (ODO vohrvor 1 00® polweree MN) hae O'6! exoacleuse (procPreudy) wii. ‎8 ‎PD‏ معاد © ان 

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ore Enzyme Core Dimer 

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4. ‏مشسا۲۰)‎ state whea DOO ot te origta oP rephooicn decuures to expose the buses, creuiay 0 rephcdion Pork. Repicoios te wudly bidrevicod Pro the prige. @. oot hos var orig, oO, whiok hos? a. © whiod sequewe of abou OPS bp required ‏له و‎ b. Three copes oP a dO-bp OT rick sequence. vc. Pow copes oP u O-bp sequews. 8. Cueds to @. cob ‏بقل‎ DOO syabests, derived Prow ta view sides (@rawe 9.8): a = @. cobs ‘ttctor poeta te Dao (Prow the dooD ww). b. OOO ketowse (Prow dou) brads tattaior proetes oo the DD®, ond ‏عمط‎ | OT ick reyon wetay OTP os oa ewer sure. v. OOO priwe (Prow coot®) birds hele to Porn o preoosowe, whick ‏هلر‎ 0 short (O-dDa) RO® prever. . 0 م © حجان 

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82 81 A 100 bp 8-24 FIGURE 8-24 Structure of replicators. The DNA clements that meke up tee well-characterized replicators are shown. The initiator DNA-binding sites are shown in green, elements that facilitate DNA unwinding in blue, and the site of the first DNA synthesis in red (the site for oni is outside the sequence shown). (2) offC is composed of four "S-mer” Dna binding sites and three "13-mer” repeated elements that are the site of initial DNA unwinding. (b) The origin of the eukaryotic virus SV40 is compesed of 4 pentarner binding sites (P) for the initiator protein called T antigen and © 20 bp cary palindrome (EP) that is the site of ONA unwinding. (c) Three elements are commonly found at S cerevisiae replicators. The A end Bt elements bind to the initiator ORC. The 62 element facilitates. DNA unwinding and binding of other replication factors. 

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E. coli “oriC” region (~250 bp] YoY “9-mers’ TGTGGATAA TTATACACA TITGGATAA TTATCCACA *13-mers’ GATCTNTTTATIT GATCTNTINTATT GATCTCTTATTAG 

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Tandem array of Binding sites for dna protein 19-mer sequences oS GATCTNTTNITIT ‘consensus ‘sequence 

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0010 Replication origin Parental sequence DNA helix (0000 2 4 Helicase denatures helix and binds with DNA @ Initiator proteins bind to replication origin primase to form primosome © Primase synthesizes RNA primer, which is extended as DNA chain by DNA polymerase ™SDNA helicase @ Helicase loads onto DNA DoonD noo E01 conan ‏مل © حجان‎ 0 

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Fig. 3.6a, b Model for the events occurring around a single replication Fira aerate Polymerase 111 9 Lagging ‘SSB (single-strand DNA binding proteins) ‏رد اه ی نوتمه‎ OWA pas primer made by ۳ DNA primase Fork : starts replication movement, st QKazaki )(۹۱۹ 6۵۲ of lagging strand fragment Polymerase III (synthesis of tat 9۳ ‘Okazaki fragment) ‏وس‎ 3 —DNA synthesized by DNA polymerase III RNA primer made by primase Polymerase III dissociates @ Discontinuous synthesis on this strand Sawn _-RNA primer for 3rd Okazaki fragment b) Further untwisting ‘and elongation of new DNA strands: 15 Okazaki 2nd Okazaki ‏سل‎ fragment elongated 2nd Okazaki fragmont elongation aa LUNN Lu 800 coooo ‏م ملاع © ان‎ 

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Single-strand gap ۳ را 5 TDS Ro* 5° 5 ۲ DNA polymerase Ireplaces th Okazaki) 1 INA primer with DNA fragment SPODDMOPD - RNA primer being replaced with DNA by polymerase I ‘5th Okazaki ۹ Gap sealed by DNA ligase none IPODODVWHYWOWPWOVHL ¢) Process continues; 2nd Okazaki fragment finished, 3rd being synthesized: DNA primase begi 4th fragment d) Primer removed by DNA polymerase I ‎Joining of adjacent‏ (و ‎DNA fragments by‏ ‎DNA ligase‏ 

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9 ‘Template stands Replication fork DNA polymerase DNA polymerase. DNA ligase 3 ‏وج‎ ho Leading strand 

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۸ B , c ۱ Phe corded PF DO grave wiow. ۲۰ ‏سم نس 206 و مت موه‎ (red), wed teP. Therwd wotra brine wher sramed, ‏مسج‎ hi fe pire ‏لت موه و جع‎ te ‏مر موی‎ trok be tewporey ceed -rrqoed, teu he bredk & reveded ( Demy, 198). epee 7a O08 vot oranion ted preveke te T-seuwed meri, fe rewire cae ‏نا قحم‎ ore tue eve ‏جد‎ (Prow onPorutos i pel ®), tue povie swerve (0), or orevtoy poome treo hoot (O) ‏سوت مس لت‎ cowpbx prochuty. 

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FINA pnmer Okazaki fragment Single-strand binding proteins DNA polymerase | Clamp Leading stand 

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۱ 9 Menement of 0 ۱۱ ‏ماس‎ ‎۱ ‎New snthesed ‏“مور‎ a leading strane Leading seand \ template DNA gyre fragment Menement of DNA pobmerase Primer Laing rand temp Primes 

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“| Unwound 1 parental ‏مس و‎ Over- wound region |) DNA gyrase cuts DNA Strands. ‎DNA rotates‏ وا ‎to remove the coils.‏ ‎1B) ONA gyrase rejoins the DNA stands 

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1. Primase synthesizes short FINA oligonucieotides (primer) ‘copied from DNA. 5 ‏سح‎ ‎primer‏ جیگ ب مت = سس ‎ONA polymerase III elongates RNA primers with new DNA,‏ .2 ‎A. 7 ‏تب تت‎ 2 ‏دن‎ ‘Okazaki fragment ‏مج 0 ‎3. DNA polymerase | removes RNA at 5’ end of neighboring fragment and fills gap. ‎ 

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4. ‏م۳‎ 2 dexntures ‏م۲ ,بر‎ Porks ae Porwed. OOO repicativd ts wsudly bi-direviivodl, but wil powder eveds ‏له‎ ‎inet oe rephodion Pork (Prepare 9.9): ORR ted ODE Pea ere Pe) at tee DDG Porwed by helicase, preveviticy ‏.جمد‎ b. Oriose syohesizes u priver va ruck tewphate strand. v. OOO powere 111 adds cuclevides to the 0" eed oP the priver, ‏لمحصاد نجه د‎ cpowplewestary to te tewphte, and displacing he G6 @s. OOO ts wade tt vpposite dreviod ve the tio tespphite strands. d. Oew strand wade S’ > 9" to sxe drevicg os wovewest oP the repicaivg Pork ts leadoy stro, while cew stro cade tt vpposte direvion ts hrgay Strood. Leudy stood ceeds cdl) oo priver, while laggy weeds o series oP prkvers. 66 مط © ان 

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6 ‏بون وجل و1‎ DO® rawses fehter wieder it per pare oP ‘ke tor chrowosowe. Bprose reliever this tewira. while hogggecy strcad t 9. beady siracd ts spohestzed prune, ‏,راص‌ممفسط اهلد‎ tn he Pora of ‏و تج‎ ‏.ص مت تا‎ OOO repicaica ts therePore 8 requires 4 priver tp bed, vod is extruded by Prager OO® pobwerer ۰ Ay ee 9 S. Okurdht dota ‏یم ها نكاد‎ wu priver, ved shou ely 4 the priver regen to the Porc oP OOO. The ack mo ۳ ween the two Preepepecs ts seded wik ODO faa. (Pry. 9. ‎GO‏ مه و ان 

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5’ TAAGGCT» AGCTA 3° 5’ TAAGGCTAGCTA 3 DNA ligase Single-strand gap Gap sealed مود وین همهم مهق ‎(oono non‏ 

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ication machine, RNA DNA polymerase IIT primer Lagging / \ strand // Okezaki fragment Template \ / 3 DNA ~_ / i 5 SSB protein = DNA primase 5 Parental هلام *3 9 DNA helicase ayo Direction of fork movement 55-58 ۱ DNA polymerase III DNA Leading strand 

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و @ Original DNA Strand 1 @ Original DNA Strand 2 © New DNA 

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Origin Anticlockwise Replication Fork ckwise Replication Fork Clockwise Anticlockwise Fork Trap Fork Trap 

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Replisome approaches. Replizome approaches nonpermissive face. permissive face. nonpemissive g nonpermissive permissive ‏ع‎ face \ Tus (7 face 08 5 Pott Ter 088 Pot! DnaB binds to Tus Arras fails and 1 and unwinding is arrested / OR \. unwinding proceeds Tun 2 ‏ار توق‎ Br Sean CRD. oo. ‘and replication continues. ‏م 4 م‎ DraB-Tus ang locked Tus-Ter ‘arrost fork 

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(. @ukervotic orig are yeorrdly oot well choractertzed) those of the peut Guockurowyoes cerevistos one uno the best urdersiood. © . Chrewrsrwd OO® Prageecis (ubru (DObp) thot are uble to replicate ugar woul) whe firoduced toto peost os extractor, vinzutar DOD ere kw os 600۲62 ‏:سجس وس سروه زاس ممموم)‎ 9. ORGs we pew repicdors. Nhe three sequewe eleweuts typicdly Pood tr DRGs we &, OA, BO, urd BO. 0۰| ‏اه‎ proteta to peosts ts the wuliproteta prigh ‏امه امس‎ (ORC), whick binds t7 @ ged Bd. Other replication protetas jot, tochuctre ver thot unvieds DOO a BC. The peust origi ‏و ها ماو اه‎ ‏مر‎ Od un BC. S. OO ued histooes woust be doubled to ‏سوه‎ vell oucte. Gd prepares the vel Por OOO repicaicd, chrowosowe duphcaivd cours duno G phos, © prepures Por cell dvisico, ond seqreyuiiva oP progeop ‏ون‎ ‎vows duray ( phos, ohowteg the cell to divide. 

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82 81 A 100 bp 8-24 FIGURE 8-24 Structure of replicators. The DNA clements that meke up tee well-characterized replicators are shown. The initiator DNA-binding sites are shown in green, elements that facilitate DNA unwinding in blue, and the site of the first DNA synthesis in red (the site for oni is outside the sequence shown). (2) offC is composed of four "S-mer” Dna binding sites and three "13-mer” repeated elements that are the site of initial DNA unwinding. (b) The origin of the eukaryotic virus SV40 is compesed of 4 pentarner binding sites (P) for the initiator protein called T antigen and © 20 bp cary palindrome (EP) that is the site of ONA unwinding. (c) Three elements are commonly found at S cerevisiae replicators. The A end Bt elements bind to the initiator ORC. The 62 element facilitates. DNA unwinding and binding of other replication factors. 

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‎pyle contol ts vowplex, ood coy vulted kere. Yeasts, tr‏ لو9.)0 ‎whick chrowesowd repiodion ts well sided, serve uo‏ من ات مرول ‏امه با ماوت رحروه ‎oP rephoutod hee tuo seporde‏ م2 ‎te cell oye,‏ محط تم موم ‎dependent hemes (Ochs) that ore‏ ‎except theta Bd.‏ ‎Te he ubsewe oP Cdsk durtay O40, rephodor selevion vows.‏ .د ‎ORO ued viker protec weewble oo euch repiodor to Prow‏ ‎b. Okeu vel ecters G phase, Odks we presen, ood urivate pre- ROs to tate ‏امه‎ ‎o. Odk witip tohbis cater round oP pre-RO ‏اس لو(‎ he vel aqatt eoters Bd, whea Odks oe ubsect. ‏0 و 9 وان 

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Lagging strand Pol a+ Primase MCM2-7 Helicase Leading strand 

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Lagging strand Replication tok = ‏الم م‎ on ee ‏و 0 سس هه‎ sa pena ماما 0 مومسم ق 

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1 Crnthea en ec occccrmCciCecrtnty Feo ter trom: Time _— Origins of replication units بسح 1 1 0:10 | | Template DNA (blue) ۱ New DNA (red) 

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و Leading. (@) DNA replication is initiated atthe ‘strand 0 ‘origin; the replication bubble grows 3 ‘as the two replication forks move in ‘opposite directions @ Finaty ony on rier nt remain ‘Sneath daughter DNA molecule © Tre ast primers oe removedby a ‏ان هل مره و و‎ 50006 polymerase can fl the rsutng gape because here Iso #-OH ‏افيه‎ ‎towhich erucoctide cen be added (@) Each round of replication generates: ‘shorter and shorier DNA molecules ‎Longa.‏ هال قلات 

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۱ ۰ ‏و وم‎ the structure ot the ead oF ear ‏من‎ chrowosowe. Centromere TL ‏لمع‎ 

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Vebwere Puccio Vebweres Puoniiva by protevitay chyowosowe ead Prow revowbicaiva, Pusioc to viker chrowvsowes, 0 low cell to diPPercoiate betwee cotucd chrowosowe pods ood dawaged DOO. Provide Deckuvisew Por Replication oP Lice DDO ads 

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Gtructure ‏عماج خأو‎ Debwere ure ‏مجلهم خام وم‎ repeus oP GO-ick OOO sequewe und telowere ‏و .مر اوه‎ the repedt is YY DOGGE, up t7 (O,OOObp ia teak. Veloweres kwe 0 9’ ‏ره لا‎ 

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۱42 کاس وج ‎ROO® ud‏ ‎Protea‏ 

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۳ the shorting ofthe chromosome strands, ia AA, | Crreescee tering eeu im _ mmm: eaten Telomerase NA template An RNA sequence In Teomerase act 8 0 template er NA, This 0 the torrets secu too 3 end of ‏سس‎ 101001 ede ‏اس لالم‎ 0 ۱ restored, Note tho gap whe the pe for ONA relation as been removed, 

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Ouique Peatuces oP teloweruse O Pwo vowpourtis---- telowerise reverse tracscriptese(TERT) proteia ced telowerise ROO O ‘eter ROD serves us tecophite Por reverse tracsvripiios by MERT O Obiliy to trcostorate ‏واه‎ the DOO 

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operon سم ‎regulator operator structural genes‏ 85 اا | a messenger RNA wn 4 repression repressor induction + messenger RNA messenger RNA 39 ١ repressor 4 } ۳ A\ proteins te, inducer-repressor complex ©1998 Encyclopaedia Britannica, Inc 

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Lac operon DNA sequences on bacterial ciromosome: Promoter for lacoperon Operator ۳ Regulat ۱۷ ‏ع‎ Zale regulatory gene ‏و‎ B-galactosidase 6 -galactoside Gene for transacetylase B-galactoside permease 

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ل د جر |r (Trp repression ‏ممه‎ leader —4 attenuator + regulatory region --+structural genes——+ high [Trp] low [Trp] attenuated mRNA VY ‏اراك‎ trp mRNA Anny 

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RNAVs.DNA * Ribose * Deoxyribose * Uracil * Thymine * Single * Double stranded stranded 

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‎is EC. cof Gubvoit Gize (BO)‏ سرام ‎٩۲۵۵‏ خام عسحلخ) ‎required Por assewbly oF the ‏و لت وه رصم‎ rexptiory proteus; ‏امه‎ ‎in vote involved in votdysis! choc initatize cod elroy ‏ها كلوط‎ the DOO ‏امس‎ ‏عرص سا تسد‎ 0 ‏مج ۳۳۳ ‎requined to restore decotured ROO poblxversse ic vir 17 its Pally Pocotiocd Pore ‎ucrtiod ‎3 999 B 98 8 ۳00۰ 6 ous oO od ‎ 

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Guapwes ud Crvterns twwolved to tracscripiiod ‏ل‎ *substrates : NTP (ATP, UTP, GTP, CTP) ‘template: DNA * enzyme: RNA polymerase * the other Protein factors 

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Chewied ‏ورام مور‎ ۲ ROO Ss. St nm, ATP + اكجوووع ( ”01 ل يمو وا سم 6۵۵ ‎nCTP‏ ‏+ ‎nyUTP‏ 5 14-3 RNA RARER ۲۵ 

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۶ ۲۱۳۶ 10 sequeuve! refers tv the pow russ TOTO, ved is kaowe us “Prbunw box”. ‎OS | refers to the‏ و۰۳ ‎PTVEOCO, whick is revoysized ‎by the 0 subuait oP ROO polyweruse, ‎ 

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eo? ot ۱ ‏هه‎ - - 4۵ a © : 8 8 re ote oP ‏واد صم‎ ‏سيا 26 عمج‎ 40 ۳۳ equa ۳۳ 229999 ‏ا‎ ‏بن 5 © © 5ق 1 ل کیب‎ 1 © 81 © ‏بن‎ ‏م‎ vi ما سس) 

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6 ١ i De votseuse (-) strand refers to the OOO strand thot is Used us tewplate to syothesize ~ROO. he seuse (+) strand oP o DOO double helix is the ooo- texpphite strocd thot hus the sawe sequeue us that oP the ROO ‏موه‎ except Por T ia pave ‏اه‎ 6۰ QOutsease (-) strand = tecphate strand Geuse (+) stroed = code strat 

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۳ ies Sida coding strand ToS 7 تل دنا 

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DNA coding strand 5’°-ATGCTA GCAGTCCACTTGTCA-3’ DNA template strand 3°-TACGAT CGTCAGGTGAACAGT-S* mRNA 5°--AUGCUAGCAGUCCACUUGUCA-3~ Protein N~Met—-Leu-Ala-Val-His—Leu-Ser-C Fig. 13-3 Relationship between the coding strand of DNA, the DNA template strand. the mRNA transcript. and the encoded protein products. 

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ROO® biosyuthesis tucludes three stayes! eitaica: ROO polywweruse bicds to the prowvter bP OOO, ued theo uo trocscripiod “bubble” te Porxved. CGboxcnitiod: he powers poze Porxutiod oP O'S -phosphodester ‏جا علدنا‎ 6 ‏رای ,سس "9ب‎ 2۲ us bulchery is. ‎whe the polywerwse reaches a‏ :بو ‎terwhdiod sequewe va DOO, the rewiivd‏ ‎stops wn the vey syokesized ROO te‏ ‎relewed.‏ 

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9( Provess vP ROO bivsvathesis: Nhe provess is sivviar tv DOO spakesis but uv priwer is weeded oad P is repkived by O. ©) Aeatratos: °0 Bator revoysizes the inittafica site [] <OG reqiva [] , the ‏روددوادها‎ oP ROO -pol bicd to duplex ODO ord wove doery the double helix tovvards —I0 reqivn. the ‏دومررصصصاصطا‎ oP ROO-pol arrived ca “10 region [] ord bied to IO region OOO is portly coed ood wos vpesed ID-CO bp ‏اما‎ 

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TTGACA 14-5 REY RNA RAMAN RIE Ri ee (۱۵ 098 2 ۲7۴ ۰۰ 8 ۴ AR 

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‎ceighbour cucleviides whick base pairs‏ 9 رو وا ‎DOO tewphte, ROO poblwercse‏ جات رجا ‎owe‏ ‎voted the Pirst polywertzatioa reuntios.‏ ‎RNARGR ‎S'-ppp® -o1 + OTP ‎-pppBpO — orp‏ © جب ‎ ‎ 

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Ribonucleoside triphosphates gran Dye 0 oN 

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Transcription « Like replication, transcription relies on base pairing. » Instead of DNA, RNA is made. » RNA is synthesized by RNA polym 

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RNA polymerase top signal for FINA polymer = DNA double helix NA HEL OPENING start site for transcription INITIATION OF RIVA CHAIN BYUOINING OF FIRST TWO RIeONUCLEOSIDE TRIPHOSPHATES RNA CHAIN ELONGATION 3 DIRECTION BYADDITION OF, RIBONUCLEOSIDE continuous BNA Strang displacement Sind ONA felix foltormation short region of ‏ام‎ TERMINATION AND. RELEASE OF POLYMERASE AND. COMPLETED RNA CHAIN 59 5 

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Transcription of RNA from DNA 5 3 DNA ۲ 6 6 ۸۵ ۸ ۲ 6۵ 6 6 ۲ ۲ ۸ ۲ 1 ۲ 6۵ 6 ۸ ‏شاه كع © اله 0 © مايه‎ ۱ Cra T 3 5 = The bottom strand of the DNA molecule above is the template for RNA synthesis. + RNA polymerase makes a copy of the DNA sequence but substitutes uridine (U) in place of thyrnine (7). TCCAATGGCTTATTTGCA direction of synthesis T A C16, G.A-A OT ALA Rie RNA + The botttom strand of the DNA duplex is used as the ternplate to synthesize RNA. However, the sequence of bases in the RNA is the same as in the top strand of the DNA, with U in place of T BNA UCCAAUGGOCUUAUUUGCA 

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TATA box start of transcription (A) )8( (۸ TFIIB 10 TFIIE_other factors 7۴۱۶ TFIH@- RNA polymerase |! (D) ۳ ATP, CTP, GTP. (E) RNA Figure 8-10 Essontial Col Biology, 26. (© 2004 Garland Scence) 

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Function Recognize core promoter, Recruit TFIIB Assist transcription activation; Assist promoter recagnition Stablize TFIID and promoter binding Recruit RNA Pol Il and TFIIF Assist RNA Pol I to reach promoter Recruit TFIIH; Modulate TFIIH helicase, ATPase and kinase activities Promoter melting using helicase activity, DNA repair iber of /Mw. (kD) ubunits TFIID - TBP 1 38 TFIID - TAFS 12 18-250 35 ,12,19 .3 : قاع TFIIB ۱ 3 1۴ 230,74 TFIIE d 2 34,57 مد 8980002 8 ره 34 32 0 * TFIIE is recruited by RNA Pol Il tModified fram: Roeder,R.G. 1996. Trends in Biochem. Sci. 21:327-334 

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| Pl fo POS TTS ene os Ere ns Lp EN a : ‏د‎ a ۰-6 es = 3 aad ‏سس‎ ‎a) ‎50 2 ‏ٌو‎ 0 v a هو هس 22 2 ۰۰-6 ,2 

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Nature Reviews | Molecular Cell Biology 

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‎reaches‏ مره ها مرن تقو (ن6 ‎the‏ وه ‎sequeue, the reyiod‏ و و ‎O’eed oF RO® Porns « kairpia structure by‏ ‎se buse-puirtay. MKe teocsvripiiva siops, the‏ ‎we releused. ‎Por those OOO texoplates that book the sequewe to produce u kairpia structure oP the RO® ‏سوم‎ o protein Pactor ocled “p ” ‏فوصت‎ كاأعر‎ 5575 trocscriptiod, wed causes releuse oP the cel spuhesized ROO. 

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© kairepic structure ut the O’ eed oF ROW G G Ce _ ‏و‎ {uuu UOH 

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مم5 

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Genes: 465 rRNARNA 235 rRNA 5S rRNA tRNA Promoters 30S pre-rRNA: | Transcription ‏و‎ 11111 1 الا ] ۱ Cleavage at t { Further trimming SS eo 16SrRNA tRNA =. 23S rRNA 5S rRNA tRNA Terminators 

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Excision of rRNAs and tRNAs from 30S precursor RNA The segment containing 16S rRNA (small ribosomal subunit) and the one containing 23S rRNA (large ribosomal subunit) are flanked by inverted repeats that form stem structure in the RNA. The stems are cleaved by RNase III. There is no apparent single sequence at which RNase III cleaves - perhaps it recognizes a particular stem structure. This plus subsequent cleavage events (by an activity called MS GeNérates the 288۴8۵6 ‏4صه‎ 235 rRNAs. The oe re also me} RNase ||| =>) <= ==> {= No apparent primary sequence specificity- perhaps RNase III recognizes a particular stem structure. (1) (2) 

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pre-tRNA in E. coli a, Sequence specific cleavage by RNases P, F, D (@) RNase P is an endonuclease that cleaves the precursor to generate the 5' end of the mature ERNA. (2) RNase F is an endonuclease that cleaves the precursor 3 nucleotides past the 3' end of the mature tRNA. (3) _ RNase Dis an exonuclease that trims in a 3' to 5' direction to generate the 3' end or the mature tRNA. ‏افصو ا‎ cca ——— 3 precursor to tRNA in E. coll RNase P 3۳ ees Becca ۳ 1 FiNase F RNase P ۳ 5 ‏تج‎ ‎J RNase F mature taNA, KA modify bases RNase D ‎con 3‏ و مهم 5 ‏ال ‎FF‏ ماله 

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RNase E and RNase III, which are endonucleases that make internal cuts in RNA molecules; * RNase II, which is an exonuclease that removes nucleotides in the 3>>5’ direction; * Polynucleotide phosphorylase (PNPase), which also removes nucleotides sequentially from the 3’ end of an mRNA but, unlike true nucleases, requires inorganic phosphate as a bo-subst=tion hairpin ae = 3 —— RNase Il, PNPase RNase E and/or 1 RNase Hl ies + ‎RNase Il, PNPase‏ هس 

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Splicing Consensus Sequences 5' Exon Intron 3' Exon 67 77 100 100 60 74 84 50 78 100 100 55 Frequency (%) copyright 1996 MW. King 

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مق ‎cleavage‏ ‎and splicing‏ exon exon mature ‏يي الملل ل‎ 

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oo 1 8 ll ‏لا‎ NTT 9 He 0-B-0-P-0-F-0-CHh OH ‏بن‎ OOH oo, Nucleobase (mPa, G,C, U) OH OH ۱ O-CH3 0=P-O——CH, oH 0 Nucleobase Q. O-(CHs or H) 0-7-8۸ OH 

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Structure of the 5’ cap on eukaryotic mRNAs. Initiating nucleotide 5' to 5' link 6 ‏وه‎ ‘in tb Can he methidatedin cap 1 SS 0 ‏بسي 6 م‎ we ‏یر‎ o> est 1 ae oer Sul A 9 8 KY ‏رن‎ ‎Ma 7 Q OCH iy Methylated in cap 2 2 ‏یمه هس‎ “ یس لا ها و ‎From GTP eA Ay‏ توهش تب "5 oon “rest of RNA 

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hydrogen bond sugar-phosphate backbone 

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1 irradiation crown — ote اد چگ a dimer residue 

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Thymine dimer ATP ADP + Pr Nicks ATP, Helicase It @— عن 00-26 5 35 م 3 ديه م @) | DNA polymerase “© | Na ligase اجبب سس 

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DNA photolyase Thymine dimer =: The photolyase recognizes and =i ‘Bing to the thymine dimer Visible light the presence oF visib Nght the enryeie eatalyyecs chemical cleavage of the Gimer. thensby restoring thormal hase paring and repairing Ure DNA. 

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© Comet of OO® ‏اه رسد‎ ‏مس‎ ارحص اص() - - ‏روما 0)00) سرا‎ se ۰) بت 

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1.DNA glycosylase recognizes Specific Damaged base ‏لبح سدح‎ 2. Cleaves glycosl bond to remoye ‘ Base 3. AP endonuclease cleaves Backbone 4. DNA Pol removes abasic site 5. Replacement of Base 

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٠ Osed by the vell Por bulky DO® ‏حول‎ ‎* Ovu spevitic DOO dawape — Chewicod adducts ... — OO photoprodurts Pirst ddeutihied ic (OOP ia C.cvh. Ludovic C. J. Gillet and Orlando D. Scharer Molecular Mechanisms of Mammalian Global Genome Nucleotide Excision Repair Chem. Rev. 2006, 106, 253-276 

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OePevis muse Xerodernd (Pigqnveuvsud - 1874, when Moriz Kaposi used this term for the first time to describe the symptoms observed in a patient.13 XP patients exhibit an extreme sensitivity to sunlight and have more than 1000- fold increased risk to develop skin cancer, especiallyin regions exposed to sunlight such as hands, face, neck Cockuwor Gyadrowe Prickothiodpsirophy 

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* OrPevts cuse ۰ Oockane Gyadowe - Asecond disorder with UV sensitivity was reported by Edward Alfred Cockayne in 1936. Cockayne syndrome CS) is characterized by additional symptoms such as short stature, severe neurological abnormalities caused by dysmyelination, bird-like faces, tooth decay, and cataracts. CS patients have a mean life expectancy of 12.5 years but in contrast to XP do not show a Clear predisposition to skin cancer. CS cells are deficient in transcription-coupled NER but are proficient in global genome NER. ° Drickothiodpstrophy 

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00 ane [۱0 ‏بوامو ماس‎ - Athird genetic disease characterized by UV sensitivity, trichothiodystrophy (TTD, literally: “sulfur-deficient brittle hair”), was reported by Price in 1980. In addition to symptoms shared with CS patients, TTD patients show characteristic sulfur-deficient, brittle hair and scaling of skin. This genetic disorder is now known to correlate with mutations in genes involved in NER (XPB, XPD, and TTDA genes). All of these genes are part of the 10-subunit transcription/repair factor TFIIH, and TTD is likely to reflect an impairment of transcriptional transactions rather than regular defect in DNA repair. This disorder is therefore sometimes referred as a “transcriptional syndrome”. 

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٠ Gteps Por DER — Revoysitica oF 008 — Excsiva ۶ 6 — Repkoewedt oF rxvived DOD 

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M13 DNA {6370 residues) —— ‏د‎ Covalent link RNA primer DNA to RNA 

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@ut-Oawer Oruce 11 Dotr-Oneer Orne M1 lydomnres (8 AWdeoavures blocks ce payee whick ooaverty the oytvstar cucevtde toto the deoxy derivative. “Ie vadhica, DOO syatherts & Purser ‏مسا لاله‎ hydroxyurea blocks the tacorporatca oP the thycotchoe cuckvtde toto ter DDO stead. 

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سج سوه (6 QOercopippurice, 0 ckewird ooddoy oP ‏وه ری عم سل‎ the: ‏ره روا ای سول اه متا‎ oe on cutest. -© ماسجا رپس با نا وی ج 10 ,نحط صا 15“ او و اه مهم سا ان اد مس و ها ماما 2 چا ای ۱0 ,ول تحطلانا) موی با لت و مان ‎syokested,‏ جه جلامه جخاصم صما جوم ها بعجاوحا برجا ‎9-OP dv works‏ ioquenosiee, readeriog the resuttoy tucker urids (DDB, RO) wouble to chrent proper proteia syoesis. تس ‎ood Oercopiepurice - Ohne fa‏ سل :مب )8 “hicquactar ts oc cotcretabolie to te syokests of ‏.وعلتمصاصه مين‎ - سوممه له عمومی؟) 

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صج معاب6 (9 Oly toy cyrus evolve reortivas wi ‏رل ۹ 00۰) با وی‎ add seth or other ‏موی اوه‎ cote wolenles where they de ont belzay. Mhis to fur tohbis their ‏ای‎ ‎wuiltzotca by bose poitoy ood causes ‏بلس و‎ of DOB. 4a he First wechaniew oo dhylatery ageot utaches dhyl yours to DO® buses. This ctheraica results to the DO betey Proqeected by repair eaayeres fa their ullewrpts to vephice the ‏و واه‎ © 1 + by waka latter, oe ee DOD decane te the Fr ‏خإم موق‎ ‏جما ها وه متا لوا رون‎ DOO. Ie this process, tue buses ‏الا و‎ ‏عا ما موه واه مه توا امه‎ 7 DO brady ses. Orves-bahiegy prevecis )000 ‏له وه با م۲‎ Por ‏هن مرو‎ traveoripion. ۳ ‏اه رتهب ع همه وه واه اه موه همست لا‎ the curtevides ‏ی وا لا‎ here or ‏ز وه وه وی اوه تاه مج بو‎ ethleckves; dhykruPocrates; ‏سح لو سور سس‎ اه مش سا وا مات ‎١‏ ددا خام عادر جد اه عاممه لاه هط ط مسر ‎this chaise. Wace hoped‏ ام عوی لح راطت او ‎ced vor or the‏ ای موه بو ‎cleave, hur‏ سا رسمه ‎thot the cower vels witht posses exaywes capable oP‏ ‎the calcercat vets.‏ دا تیه مق لوف ‎vesltiog tothe selecive productoa of oc‏ ‎Ovxepare the top ood botiow structures fa the graphic vo the bePt.‏ Otroges Ousted oad Opclesporamide - Okie to ‏سحن نجه‎ 

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۱ 000) با اما ری ری روما موعل ,منیب تاه مسلفی خن جانمی 4 افص ت 6100 هه سره سا معط ‎cand keane‏ 0 wt DOO ka a varey oP dPPeret une raokacky nteroduiza ‏ها سوه‎ he beer pire), DOO otrernl bred ace ‏ویس سا لت میلگ‎ ‏سور‎ 1, Dont oP heoe oouqmarnts kuve ber bokted Prox ‏ستهمافي لمت صصح لصهي‎ ‏تسا‎ hey kok he peat oP he oakiiorobad extbetos orl hue proche ok ‏رها‎ ‎Dixon uber utd weed Por fae‏ ,سنارت ‎drag‏ هه ‎ore ex fie covet Krpork‏ وروی تب ‎renin oP several ook‏ ‏ما ان تم ‎hie davcer bers onl Korvbes are word ecko Por the‏ جرد ‎‘Dheoe execs have a ‏جعاتيهي‎ oP ‏تيمطماهم صتمكلاك نموت‎ Mterodkscn (oovewaty bet vera tue bee ptr) tak OOO WPeokny wary Patee oP he DDO tehadery DOD xed ROO syrtheots. Dredhune oP he O00 viral oxi doy ooo by kiibiiva oP ‏هت وروی بو‎ ‏لت سنج وا ‎Orrxorubtcta - Ober‏ ‎Dauner ubicta - Ohne to ce utero ‎O):‏ سوسه) مرسمه ‎6 ‏ول ون تط‎ khbts DOD drevied 6۱۵ ‏هت لاف ای سره‎ 0 orrtheots ‏تن رد () الا صحف ص‎ ROO we ‏ام قح ,لاف‎ ROO tw wore sewee. Daren ‏با مها‎ debe stron (DODO , perseatert RDO chs Rates bus booker chs renter. Dr he OCD cepeenks oa he preveure oP qc. ‎ter aru wird‏ وان - 0) سونو ‎Diaks to Obtere: Bottarenyota ~ cetaky of ‏اه‎ ‎sks» Obnoe: ‏رت روهظ‎ DOO ‎ 

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6( 0 Dierwpters: (Phot dkobids the ‏رد اه سم عون‎ or cwiosis. kere ore severd poses of wwii, cae oP hick te the c7etaphusr. Durty wetuphose, he vel puls duptoced DDB + to vther side of he parrot oell kt ‏هط تساه مصصص‎ posure thot pack vow oll yet o Pull set of OO. Opies are cioroibuker Phere Porcoed ‏مس تا اه چا با رن‎ “iubul!". Orso bias ty tubule, thus prevecitery tre Prrwratoa of spider ced cell visio. ‎Chieoe is eu wierd‏ + موه ‎Tol: ‎(Parkin (rol) ue Pirst tsvkied Pro the Proc the bork of he PorPir ew (Tome brevPoba). Docetaxel is 3 c7ore puted ued hal is procured secrisycihetrdly. ‎115 oerirast to vker sniorotubuke octagpaists, keel drupe he equibriucr between Pree tubal ‏لمم‎ ‏روا لطس‎ shPiee tic the drevion oP assembly, raker thos doassewbly. Bs resuk, ‏ماه اما موه نمی ام‎ oP ‏طسو‎ ued the Porto oP oboe ‎] oP cwioroibules. (Nhe vet oPPent ‏جا‎ otll he der upiors ‏صوصب خان‎ ‎eu ied‏ و سا - ام( ‎ ‎ 

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Vincristine C. Ophardt, . 2003 

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۱ “hierar Boru! Aeterookton opus Werke betvern buses Ubon he DOO. The tterockted deny sore des oP Pent the siructee of he OOO, prevent pobweree od ver DOD birch proteker ‏روط مس‎ propery. Phe resul is preveciirs oP OO® syakests, ‏متام‎ of 0 oer تبسن له ملاسما امه ۳ ‏اس اوه مومت لا‎ to OO wk prePereatd brace t7 te (D-P postion of ‏من‎ a odeuke. Dhey ore cble ty bid to too dered ster oa OO ® product ores tohe, ether hirestrand (wikia he sare DO woke which rewule ‏مت جا‎ of DDB ‏سوه ور‎ seed serra, ‎ord Oarbopkata - Oboe ta ey wierd‏ لب