Chng 2

Cu trc v chc nng ca gene Nhim sc th cha DNA (deoxyribonucleic acid) mang gene. Gen

c truyn t b m sang con ci v c xem l n v c bn ca s di truyn, nh hng ln mi cu trc v chc nng ca c th. ngi c khong t 30.000-40.000 gene cu trc (gene m ha cho RNA hoc cc protein). I. Cu trc ca DNA 1. Thnh phn ha hc v cu trc khng gian ca DNA

Phn t DNA c cu to t cc n phn l nucleotide. Mi nucleotide c 3 thnh phn c bn: (1) mt ng pentose deoxyribose; (2) mt nhm phosphate v (3) mt trong bn loi base. Hai loi base cytosine (C) v thymine (T) c cu trc vng n carbon nitrogen c gi l cc pyrimidine. Hai loi base adenine (A) v guanine (G) c cu trc vng kp carbon - nitrogen c gi l cc purine (hnh 1).

Tn ca cc loi base c dng t tn cho cc nucleotide.

Hnh 1. Cu trc ca 4 loi base

DNA c cu trc khng gian nh mt thang xon vi 2 tay thang l cc phn t ng v phosphat ni vi nhau bng cc lin kt phosphodiester bn vng, bc thang do cc base hai bn ni vi nhau qua cc lin kt hydro yu theo nguyn tc b sung gia base adenine vi thymine v gia base guanine v cytosine. Mi tay thang bt u t v tr 5, kt thc v tr 3 ca phn t ng deoxyribose v hai tay thang i ngc chiu nhau. Nh vy nu mt chui n ca DNA c trnh t cc nucleotide 5 - ATGCAG - 3 th chui b sung s c chiu v trnh t ca cc nucleotide nh sau:

Hnh 2. Cu trc xon kp ca DNA

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NGUYEN TUNoteNU

3 - TACGTC - 5 (hnh 2). Cc trnh t khc nhau ca cc nucleotide s quy nh cc loi

protein khc nhau. Tnh c hiu ca nhiu loi protein trong c th i hi phi c mt lng ln thng tin di truyn. Thc t trong b NST n bi ca cc giao t ngi cha ti khong 3 t cp nucleotide, s lng ny nhiu hn nhiu so vi s nucleotide cn thit cho vic m ha cc protein ca c th. 2. Hin tng cun xon ca DNA

Tng chiu di ca DNA trong mt t bo khong 2 mt do c th nm gn trong nhn t bo DNA phi cun li nhiu mc khc nhau (hnh 3). u tin cc oan DNA vi chiu di tng ng vi khong t 140 n 150 cp base (base pair: bp) cun quanh mt li protein histon to thnh nucleosome. Cc nucleosome ni vi nhau bng mt on DNA khong 20 - 60 bp. Khong 6 nucleosome cun li thnh mt solenoid, cc solenoid cun li thnh cc quai chromatin (chromatin loop), mi quai chromatin c khong 100.000 bp

(100 kb). Cc quai ny c gn vi mt khung protein. Bng cch ny DNA c th gim chiu di xung khong 1/10.000 ln so vi chiu di ca n trc khi cun xon.

Hnh 3. M hnh cun xon ca DNA

II. Cu trc ca gene 1. Cc intron v exon

Cu trc intron v exon ca gene l mt c im phn bit gia DNA ca sinh vt eukaryote v prokaryote. Cc intron chim phn ln trong cu trc hu ht cc gene ca c th eukaryote. Cc on intron ny

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s c cc enzyme ct mt cch chnh xc ra khi cc phn t mRNA trc khi chng i ra khi nhn t bo. V tr ct ca cc enzyme c xc nh bi cc on DNA c gi l cc on ng nht (consensus sequences) (on ny c tn nh vy v c thy ph bin tt c cc c th eukaryote) nm cnh mi on exon (hnh 4).

Hnh 4: Cu trc chi tit ca mt gene V hu ht cc gene ca c th eukaryote gm ch yu l cc on

intron nn cho php ngi ta ngh n vic cc on ny c th c mt chc nng no . Hin nay chc nng ca cc intron vn cn ang c nghin cu, ngi ta cho rng c th nhng on intron do lm tng thm chiu di ca gene s to thun li cho s ti sp xp ca cc gene trn cp NST tng ng qua qu trnh trao i cho gia cc NST ny trong gim phn hoc nh hng n thi gian nhn i v phin m ca DNA.

Mt s intron li mang trong n cc gene c phin m m khng lin quan g ti chc nng gene mang chnh cc intron . V d nh cc intron trn gene gy bnh u x thn kinh type 1 (NF1) cha 3 gene c phin m theo hng ngc vi gene NF1 v khng c mi lin h chc nng no vi gene NF1. 2. Cc loi DNA

Mc d DNA mang thng tin m ha cho cc protein nhng trong thc t ch c t hn 5% trong s 3 t cp nucleotide trong genome ca ngi thc s lm chc nng ny, cn li phn ln vt liu di truyn cha c bit chc nng. Ngi ta chia DNA thnh cc loi sau: 2.1. DNA c bn (single - copy DNA):

DNA c bn chim khong 45% genome v gm cc gene m ho cho cc protein. Cc on DNA loi ny ch c thy mt ln duy nht (hoc vi ln) trong genome. Tuy nhin phn m ha cho protein ch chim mt phn nh trn loi DNA ny m thi, phn ln cn li l cc intron hoc l cc on DNA nm xen gia cc gene. 2.2. DNA lp (repetitive DNA):

DNA lp chim 55% cn li ca genome, y l cc on DNA

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c lp i lp li c th ln ti hng ngn ln trong genome, c 2 loi chnh: 2.2.1. DNA v tinh (satellite DNA) Loi DNA ny chim khong 10% genome v tp trung mt s vng nht nh trn NST, chng sp xp ni ui nhau, ci ny tip theo ci kia. DNA v tinh c chia thnh 3 loi nh: - DNA v tinh alpha: c kch thc 171 bp, lp i lp li nhiu ln vi

chiu di hng triu bp hoc hn. Loi ny c thy cnh tm ng ca NST.

- DNA tiu v tinh (minisatellite DNA): c kch thc t 14 - 500 bp, lp i lp li vi chiu di khong vi ngn bp.

- DNA vi v tinh (microsatellite DNA): c kch thc t 1 - 13 bp, lp i lp li vi tng chiu di khng qu vi trm bp.

Hai loi DNA tiu v vi v tinh c s khc nhau rt ln trong chiu di gia ngi ny vi ngi khc v iu ny lm chng tr nn rt hu ch trong vic lp bn gene. DNA tiu v tinh v vi v tinh c gp vi tn s trung bnh l 1 trn mi 2 kb trong genome v chng chim khong 3% genome. 2.2.2. DNA lp li ri rc: Loi DNA ny chim khong 45% genome, gm 2 loi: - Cc yu t ri rc c kch thc ngn (SINEs: short interspersed

elements): kch thc t 90 - 500bp. - Cc yu t ri rc c kch thc di (LINEs: long interspersed

elements): kch thc 7.000 bp III. Chc nng ca DNA 1. S nhn i

S nhn i ca DNA khi t bo phn chia gip to ra cc bn sao chnh xc ca DNA cho cc t bo con, m bo cho vic duy tr vt cht di truyn n nh qua cc th h t bo.

S nhn i ca DNA bt u bng vic ph v cc lin kt hydrogen yu gia cc base, lm tch cu trc kp ca DNA thnh 2 si n vi cc base trng thi t do. Mi si n s ng vai tr nh mt khun (template) v cc base ny s lin kt vi cc base ca cc nucleotide t do theo nguyn tc b sung gip qu trnh nhn i din ra chnh xc. Bng cch ny sau khi hon tt qu trnh nhn i mi DNA s gm c mt chui n c v mt chui mi c tng hp. Phn t DNA

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mi ny c cu trc ging ht DNA ban u (hnh 6).

Hnh 6. S nhn i ca DNA Qu trnh nhn i ca DNA c xc tc bi nhiu loi enzyme

khc nhau, mt enzyme xc tc cho vic tho xon, mt enzyme khc xc tc cho vic tch DNA thnh 2 chui n, v mt s enzyme khc thc hin nhng chc nng khc nhau trong qu trnh nhn i. DNA polymerase l mt trong s cc enzyme chnh phc v cho qu trnh nhn i, di chuyn dc theo si n DNA t u 3 n u 5 v gn cc nucleotide t do theo nguyn tc b sung vo si n DNA bng cch gn chng vo u 3 ca chui polynucleotide ang c tng hp. Do si DNA n mi lun lun c hnh thnh theo chiu t 5 n 3 v qu trnh nhn i trn 2 mch ca phn t DNA m s din ra theo hai chiu ngc nhau.

Ngoi vic gn cc nucleotide, enzyme DNA polymerase cn thc hin vic kim tra xem mt nucleotide mi c b sung chnh xc vi nucleotide trn mch khun khng, nu khng th nucleotide ny s b loi b v thay bng mt nucleotide khc. Qu trnh ny gip m bo cho s nhn i ca DNA din ra mt cch chnh xc. Nu mt sai st trong qu trnh nhn i khng c sa cha thnh cng s lm xut hin t bin v cc t bin ny c th s dn n cc bnh di truyn.

Tc nhn i ca DNA khong 40 - 50 nucleotide / giy. Tc ny chm hn nhiu so vi tc nhn i vi khun vi 500 - 1000

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nucleotide / giy. c th thc hin nhn i mt cch nhanh chng DNA (mt vi NST c khong 250 triu nucleotide), s nhn i xy ra ti nhiu im khc nhau trn DNA, nhng v tr ny c gi l cc im gc nhn i (replication origins). Cch nhn i nh vy s to ra nhiu ch tch trn chui DNA, nhng ch c gi l cc vng nhn i (replication bubble) v pha xy ra hng pht trin s nhn i ca vng nhn i ny c gi l chc nhn i (replication fork) (hnh 7).

Hnh 7. S hnh thnh cc vng nhn i gip qu trnh nhn i din ra nhanh hn

2. Qu trnh phin m Qu trnh phin m (transcription) gip truyn thng tin di truyn

cho vic tng hp protein t gene trn DNA trong nhn i vo bo tng tham gia vo qu trnh tng hp protein. Qu trnh ny c thc hin thng qua phn t RNA.

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RNA cng l mt loi acid nucleic c cu trc tng t DNA vi cc phn t ng, nhm phosphate v nitrogenous base tuy nhin thay cho ng deoxyribose l ng ribose, v thay cho thymine l uracyl. Uracyl c cu trc tng t thymine nn c th bt cp vi adenine. Mt im khc bit quan trng na l RNA thng ch c cu trc si n thay v si kp nh DNA.

Qu trnh phin m tng hp nn loi phn t RNA thng tin (mRNA: messenger RNA) t bn khun trn DNA (hnh 8).

1. Bt u cho qu trnh phin m mt trong s cc enzyme RNA polymerase ( RNA polymerase II) s gn vo mt on DNA nm pha trn gene gi l v tr khi ng (promotor site). Di s xc tc ca enzyme ny cu trc xon kp ca mt on DNA s c tch i v mt trong hai mch ca DNA s ng vai tr ca bn khun tng hp mRNA.

V tr khi ng ng vai tr quyt nh mch no s tr thnh mch khun trong vic tng hp mRNA thng qua vic nh hng cho enzyme RNA polymerase trn DNA. Trn mch khun, RNA polymerase s di chuyn theo chiu t 3 n 5 v cho php cc lp ghp cc ribonucleotide theo nguyn tc b sung theo chiu t 5 n 3 vi cc base trn mch khun theo cch thc tng t nh trong qu trnh nhn i ca DNA nhng base thymine c thay bng uracyl.

Hnh 8. Qu trnh phin m trn DNA

2. Sau khi qu trnh tng hp RNA c bt u, u 5 ca phn t RNA ang c tng hp s c bt li bng cch thm vo mt

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nucleotide guanine c thay i v mt ha hc u ny c gi l 5 cap. 5 cap gip ngn cn s ging ha ca RNA trong qu trnh tng hp v gip ch nh v tr bt u qu trnh gii m ca mRNA.

3. Qu trnh phin m c tip tc cho ti khi RNA polymerase c ti mt on nucleotide gi l on kt thc (termination sequence). Khi n v tr ny mt on gm t 100 n 200 adenine s c gn vo u 3 ca mRNA, cu trc ny c gi l ui poly - A (poly A-tail). ui poly-A c cho l c vai tr gi cho phn t ny c hng nh v khng b ging ha khi vo trong bo tng. Khi n v tr kt thc, RNA polymerase tip tc phin m trn chui DNA thm vi ngn base tuy nhin trn mRNA on base thm pha sau ui poly - A s b mt i.

4. Cui cng RNA polymerase s tch khi chui DNA, gii phng phn t RNA vi cu trc chui n, phn t ny c gi l phn t m sao nguyn thy (primary transcript).

mt s gene ngi, trn mt gene c th c nhiu v tr khi u khc nhau nm cc v tr khc nhau do lm gene c th c bt u phin m cc v tr khc nhau dn