ADNmonocatenar(mc)

unelevirusuri,deex.parvovirusuri

ADNdublucatenar(dc)

circularcircular

linearlinear

Cromozombacterian,Plasmidebacteriene

Cromozomidelaeucariote

ADNdcADNdccircularcircular

delavirusulSV40delavirusulSV40 ADNdcADNdccircularcircular

dinmitocondriiumanedinmitocondriiumane

ADNdclinearumaninreplicareADNdclinearumaninreplicare

De la ADN la cromozomiDe la ADN la cromozomi

Unelevirusuri

ADNmitocondrial,ADNcloroplastic

CromozomlaCromozomlaE.coliE.coli

PlasmidelaPlasmidelaE.coliE.coli

Unelevirusuri

Cuvntulcromozom:chroma

=culoare,soma

=corp cromozom=corpcolorat

n celule, moleculele de ADN sunt asociate cu proteinen celule, moleculele de ADN sunt asociate cu proteine

Fiecare molecul ADN Fiecare molecul ADN + proteinele asociate = cromozom, + proteinele asociate = cromozom, i la PK, i la PK, i la EK i la EK

mpachetareaADNmpachetareaADNuluiuluincromozomincromozomindeplinendeplinetemaimultefunctemaimultefuncii:ii:

ADNADNulcelulararedimensiunemaimaredectcelulaulcelulararedimensiunemaimaredectcelula ptraptrancpeancpeancelulncelul,ADN,ADNultrebuiecompactatultrebuiecompactat

mpachetareaADNmpachetareaADNuluiuluiiasociereacuproteineprotejeazfaiasociereacuproteineprotejeazfadealterridealterri

DoarDoarnformcompactatnformcompactatncromozomi,ADNncromozomi,ADNulpoatefitransmiseficientulpoatefitransmiseficientiegallacele2celulefiiceiegallacele2celulefiice

ADNADNulnudestedestuldeinstabilulnudestedestuldeinstabilncelule,spredeosebiredecromozomi,caresuntmultmaistabilncelule,spredeosebiredecromozomi,caresuntmultmaistabilii

CrzconferoorganizareglobalfiecreimoleculedeADNCrzconferoorganizareglobalfiecreimoleculedeADN,o,organizarececonferrganizarececonferiaccesibilitatectreADNiaccesibilitatectreADN

De la ADN la cromozomiDe la ADN la cromozomi

dinmasaunuicrzEK=proteinedinmasaunuicrzEK=proteine CromatinCromatin=regiunidinADNasociatecuproteine=regiunidinADNasociatecuproteine

MajoritateaproteinelorasociatecumoleculeledeADN=proteineMajoritateaproteinelorasociatecumoleculeledeADN=proteine

cug.m.cug.m.mmicic,bazice,bazice

HISTONEHISTONEAlteproteineasociatecuADN:AlteproteineasociatecuADN:NONNONHISTONEHISTONEregleazreplicarearegleazreplicarea,repararea,recobinarea,repararea,recobinareaitranscriereaitranscrierea

PrimulrolimprotantalproteinelorasociatecuADN,PrimulrolimprotantalproteinelorasociatecuADN,nmodspecialalhistonelor,estecompactareamoleculelordeADNnmodspecialalhistonelor,estecompactareamoleculelordeADN

Deex:Deex: grosimeamedieauneipb=3,4grosimeamedieauneipb=3,4

1c1celulumanconelulumanconine3x10ine3x1099

pb/sethaploid,pb/sethaploid,~ ~ 10101010

~ ~ 1m1m 1cel.are1cel.arennucleu(nnucleu(

=10=1015mm)2mdeADN15mm)2mdeADN

MajoritateaPKau1cromozomMajoritateaPKau1cromozom=1=1moleculdeADNdmoleculdeADNd.c.circular.c.circular

OrganismeleseOrganismelesenmulnmulescprindiviziunecelularsimplescprindiviziunecelularsimpl

fisiunebinarfisiunebinar

Fiecare celul are un anumit numr, specie-specific, de cromozomi

PK PK

EK EK

CromozomulbacterianCromozomulbacterian

nucleoidnucleoid

NuexistmembrannuclearNuexistmembrannuclearnuexistnucleunuexistnucleu

PKpotaveaPKpotaveaiplasmide(moleculeADNdc,deobiceicirculare)iplasmide(moleculeADNdc,deobiceicirculare)

MajoritateacelulelorEKsuntMajoritateacelulelorEKsuntDIPLOIDEDIPLOIDE:aucte2exemplaredinfiecarecrz,darcele2exemplarenus:aucte2exemplaredinfiecarecrz,darcele2exemplarenusuntidenticeuntidentice

DiploidiaasigurDiploidiaasigurnmulnmulireadetipsexuatireadetipsexuat

aorganismelorEKaorganismelorEK

gamegameiiauiiau

nr.crznr.crz

NumrpardecromozomiNumrpardecromozominnucleu(nnucleu(2n),2n),fiecarecrz=1molfiecarecrz=1moleculADNdeculADNd.c.linear.c.linear

OrganismeleEK(majoritatea)seOrganismeleEK(majoritatea)senmulnmulescprinreproduceresexuatescprinreproduceresexuat

Celule2nCelule2n GameGameiinnmeiozmeioz fecundafecundaieie

unireaa2gameunireaa2gameii Celule2nCelule2n

nmitocondrii,cloroplastenmitocondrii,cloroplaste

cte2cte210moleculeADNdccircularADNmt10moleculeADNdccircularADNmt

ADNextracromozomal:ADNextracromozomal:

ADNextracromozomal:ADNextracromozomal:

(cte1exemplardinfiecaretipdecrz)

p l i e r e

su p r a r a su c i r e

c i r c a 5 0 d o m e n i ip e r c r o m o so m

b a c t e r i a n

c r o m o so mb a c t e r i a n

d o m e n i isu p r a sp i r a l i z a t e

n e g a t i v

R E P

R E P

A D N g i r a z a

Cromozomul la procariote PK

proteine histonehistone--likelike

: HU (Helix-Unwinding)

Cromozomul la eucariote

Dimensiune genom Dimensiune genom [Mpb] [Mpb] Forma crzForma crz

Nr.crz. /Nr.crz. /set haploidset haploid

Nr.seturi Nr.seturi haploidehaploide

Nr.total Nr.total crzcrzSPECIESPECIE

P R O C A R I O T EP R O C A R I O T E

4,64,6circularcircular111111Escherichia coliEscherichia coli

2,82,8circularcircular111111Staphylococcus aureusStaphylococcus aureus

circularcircular221122Vibrio choleraeVibrio cholerae

5,75,73 C, 1 L3 C, 1 L441144Agrobacterium tumefaciensAgrobacterium tumefaciens

E U C A R I O T EE U C A R I O T E

12,112,1linearlinear16161 sau 21 sau 23232Saccharomyces cerevisiaeSaccharomyces cerevisiaedrojdia de beredrojdia de bere

9797linearlinear66221212Caenorhabditis elegansCaenorhabditis elegans

125125linearlinear55221010Arabidopsis thalianaArabidopsis thaliana

15 00015 000linearlinear88221616Allium cepaAllium cepa

45004500linearlinear77221414Pisum sativumPisum sativummazremazre

180180linearlinear442288Drosophila melanogasterDrosophila melanogaster

26002600linearlinear2020224040Mus musculusMus musculus

25002500linearlinear1919223838Felis catusFelis catuspisica domesticpisica domestic

24002400linearlinear3939227878Canis familiarisCanis familiariscinecine

27002700linearlinear1919223838Sus scrofaSus scrofaporc domesticporc domestic

27002700linearlinear2727225454Ovis ariesOvis ariesoaieoaie

29002900linearlinear3030226060Bos taurusBos taurusvaca domesticvaca domestic

26002600linearlinear3232226464Equus caballusEquus caballuscalcal

29002900linearlinear2424224848Gorilla gorillaGorilla gorilla

33003300linearlinear2424224848Pan troglodytesPan troglodytes

32003200linearlinear2323224646Homo sapiensHomo sapiens

Organismelemaicomplexeaudensitategenicsczut

NUCLEOZOMULNUCLEOZOMUL

nceluleleEK,nceluleleEK,majoritateacantitmajoritateacantitiiADNesteiiADNestempachetatmpachetatnnNUCLEOSOMINUCLEOSOMINucleosom=miezde8proteinehistonice+regiuneaADNNucleosom=miezde8proteinehistonice+regiuneaADNnfnfuraturatnjurullornjurullor AspectdemrgelepeunfirAspectdemrgelepeunfir

ADNADNuldintre2nucleosomiadiacenuldintre2nucleosomiadiaceni=i=ADNlinkerADNlinker(de(delegturlegtur))

Prinasamblare/Prinasamblare/mpachetarempachetarennucleosomi,nnucleosomi,ADNADNulsescurteazdeulsescurteazde6ori6ori

Asamblarea/Asamblarea/mpachetareampachetareannucleosomi=nnucleosomi=primaetapprimaetapieseniesenialialncompactareaADNncompactareaADNuluiului

H2AH2A

H2BH2B

H3H3

H4H4

ADNADNnfnfuraturatnjurulunuioctamerhistonicnjurulunuioctamerhistonic~~147pb,de1,7ori147pb,de1,7ori

HistoneHistonele=proteinemici,le=proteinemici,ncrcatepozitivncrcatepozitiv

HistoneleHistonele

=celemaiabundenteproteineasociatecuADNlaEK=celemaiabundenteproteineasociatecuADNlaEK

5tipuri:5tipuri:

H1,H2A,H2B,H3,H4H1,H2A,H2B,H3,H4

histonelemiezhistonelemiez

2x[H2A,H2B,H3,H4]=MIEZULNUCLEOSOMULUI2x[H2A,H2B,H3,H4]=MIEZULNUCLEOSOMULUI

1x1xHH1s1seleaglaADNeleaglaADNullinker,dintre2nucleosomiullinker,dintre2nucleosomi

proteinemici,proteinemici,ncrcatepozitivncrcatepozitiv(con(coninutridicatinutridicatnAAnAAncrcatpozitivncrcatpozitiv))

111115KDa15KDa

H2H2H4H421KDa21KDa

H1H1

MiezulproteicalnucleosomuluiareformdediscMiezulproteicalnucleosomuluiareformdedisc

nsolunsoluie,cie,cele4tele4tipuridehistoneseasambleazastfelipuridehistoneseasambleazastfel::

H2A+H2BH2A+H2B heterodimerH2AheterodimerH2AH2BH2B

H3+H4H3+H4 heterodimerH3heterodimerH3H4H4

2heterodimeriH32heterodimeriH3H4H4 tetramerH3tetramerH3H4H4

AsamblareaunuinucleosomesterealizatAsamblareaunuinucleosomesterealizatntrntroanumitordineoanumitordine::

H3+H4H3+H4 heterodimer[H3heterodimer[H3H4]H4]

2x[H32x[H3H4]H4] tetramer4[H3tetramer4[H3H4]H4]

1tetramer4[H31tetramer4[H3H4]seataH4]seataeazlaADNeazlaADN

2heterodimeri[H2A2heterodimeri[H2AH2B]seataH2B]seataeazlaacestcomplexeazlaacestcomplex

NUCLEOSOMNUCLEOSOM

H2A+H2BH2A+H2B heterodimer[H2Aheterodimer[H2AH2B]H2B]

1.Dimerizareahistonelor1.Dimerizareahistonelor

2.Ini2.Iniiereanucleosomuluiiereanucleosomului

3.3.TerminareaformriinucleosomuluiTerminareaformriinucleosomului

H2AH2A

H2BH2B

H3H3

H4H4

STRUCTURACROMATINEISTRUCTURACROMATINEI EucromatinEucromatinaaiHeterocromatinaiHeterocromatina

HistonHistonaa

H1H1seleaglaADNlinkerdintrenucleosomiseleaglaADNlinkerdintrenucleosomi

OdatformaOdatformainucleosomii,inucleosomii,urmtareaetapurmtareaetapnnmpachetareamoleculelormpachetareamoleculelor

deADN=legareahistoneiH1deADN=legareahistoneiH1

H1H1=o=oproteinmicproteinmic,,ncrcatpozitivncrcatpozitiv,s,seleaglaADNeleaglaADNuldintrenucleosomiuldintrenucleosomi

nacestmod,nacestmod,HH1s1stabilizeazasociereaADNtabilizeazasociereaADNuluicuproteineleuluicuproteinele

nucleosomalenucleosomaleideci,ideci,stabilizeazstructuranucleosomuluistabilizeazstructuranucleosomului

SeleaglaADNSeleaglaADNn2zone:n2zone:

ozonesteexactozonesteexactnafaraunuinucleosomnafaraunuinucleosom

ozonesteregiuneacentraldeozonesteregiuneacentraldenfnfurareaADNurareaADNnjurulhistonelormieznjurulhistonelormiez

secoloreazmaislabsecoloreazmaislab

estemaiactivcaratdetranscriereestemaiactivcaratdetranscriere

secoloreazmaiintenssecoloreazmaiintens

estemaipuestemaipuinactivcaratdetranscriereinactivcaratdetranscriere

Chiar i n interfaz, nu toat cromatina are acelai grad de condensare :

n interfaz

materialul genetic

: -

este structurat sub form de CROMATIN-

cromozomii nu sunt

vizibili la microscop

Cele 23 de perechi de cromozomi umani ocup anumite teritorii n nucleu

EUCROMATINAEUCROMATINA HETEROCROMATINAHETEROCROMATINA

AdugareahistoneiHAdugareahistoneiH11 unnivelsuperiordecompactareaADNunnivelsuperiordecompactareaADNuluiului

UrmtoareaetapdecompactareUrmtoareaetapdecompactare=FIBRADE30nm=FIBRADE30nm EvidenEvideniatiatiiinvitroinvitro

iiinvivoinvivo

2m2modeledestructurafibreideodeledestructurafibreide30nm30nm

ModelulModelulSOLENOIDSOLENOID SeformeazunsuperhelixceconSeformeazunsuperhelixceconine6nine6nucleosomiperspirucleosomiperspirADNADNullinkersegseullinkersegsetespreinteriorulsuperhelixului,darNUtreceprinaxulcentratespreinteriorulsuperhelixului,darNUtreceprinaxulcentralalacestuialalacestuiaZoneledeZoneledeintrareintrare

iiieieireire

aADNdinnucleosomiNUsuntaccesibileaADNdinnucleosomiNUsuntaccesibile

ModelulModelulZIGZAGZIGZAG

ADNADNullinkerTRECEprinaxulcentralalsuperhelixuluiullinkerTRECEprinaxulcentralalsuperhelixului

accesibileaccesibilemaimaiaADNdinnucleosominusuntaADNdinnucleosominusuntireireieieiiintrareintrareZoneledeZonelede

SeformeazunsuperhelixceconSeformeazunsuperhelixceconine4nine4nucleosomiperspirucleosomiperspir

LungimeaADNLungimeaADNuluilinkeruluilinker

variazvariaz(distan(distanaa

dintre2nucleosomi)dintre2nucleosomi)

RegiunileculinkermailungRegiunileculinkermailung

(deci(decicudensitatemaicudensitatemai

micdenucleosomimicdenucleosomi)a)aii

fibreide30nmfibreide30nmauau

structurZIGZAGstructurZIGZAG

ntrntrunacelaunacelainucleuseinucleuse

potpotntlnintlninsimultannsimultan

ambeleformeambeleforme

RegiunileaminoRegiunileaminoterminalealehistonelorsuntnecesareptrformareafibrei30nmterminalealehistonelorsuntnecesareptrformareafibrei30nm

CozileaminoCozileaminoterminalealehistonelornucleosomale(H2A,H2B,H3,H4)interacterminalealehistonelornucleosomale(H2A,H2B,H3,H4)interacioneazcunucleosomiiadiacenioneazcunucleosomiiadiacenii

UrmtoareaetapUrmtoareaetapncompactareaADN=formareadebuclemarincompactareaADN=formareadebuclemari

Formareanucleosomilor+formareafibrei30nmFormareanucleosomilor+formareafibrei30nm compactareaADNcuscurtarepcompactareaADNcuscurtarepnladenlade40deori40deoriEsteEstencinsuficientncinsuficientestenecesarcompactareamaiputernicaADNestenecesarcompactareamaiputernicaADNModel:Model: Fibra30nmFibra30nmformeazbuclemariformeazbuclemari,de40,de4090kpb,90kpb,inutedeostructurproteicdenumitNUCLEARSCAFFOLDinutedeostructurproteicdenumitNUCLEARSCAFFOLD

(traducere(traducereadliteramadliteram:s:schelnuclearchelnuclear))

2clasedeproteine:2clasedeproteine:TopoIITopoII:l:labazafiecreibucleabazafiecreibucle,men,menineformabuclatineformabuclat;buclelesunttopoizomeri;buclelesunttopoizomeri

ProteineSMC(StructuralMaintenanceofChromosome)ProteineSMC(StructuralMaintenanceofChromosome)

SeformeazfibradecromatinSeformeazfibradecromatin=s=structurdebazacromozomilortructurdebazacromozomilor

MBOGMBOG

NucleosomeAssemblyNucleosomeAssembly

StructuracromozomilorseschimbdeStructuracromozomilorseschimbdealungulcicluluicelularalungulcicluluicelular

GraduldecondensareamaterialuluigeneticvariazGraduldecondensareamaterialuluigeneticvariazntimpulunuiciclucelularntimpulunuiciclucelular

InterfazInterfazcondensaremairedusamaterialuluigeneticcondensaremairedusamaterialuluigenetic,permitetranscriere,replicare,reparare,permitetranscriere,replicare,reparare

DupreplicareDupreplicare,moleculelefiice:,moleculelefiice:

asamblarenucleosomiasamblarenucleosomi

coeziuneacromatidelorsuroricoeziuneacromatidelorsurori

complexproteicdenumitcomplexproteicdenumitcoezincoezin

formareafibrei30nmformareafibrei30nm

ninterfaznusevdcromozomiicaentitninterfaznusevdcromozomiicaentitidistinctecitologic;suntvizibiledoarblocuricromaticeidistinctecitologic;suntvizibiledoarblocuricromaticecromatincromatin,,

unelecoloratemaislabunelecoloratemaislabeucromatineucromatin,a,altelecoloratemaiintensltelecoloratemaiintensheterocromatinheterocromatin

ProfazProfazcontinucondensareacromatineicontinucondensareacromatinei(deci,amaterialuluigenetic)(deci,amaterialuluigenetic)

(procesulsemainume(procesulsemainumeteteiicondensareacromozomilorcondensareacromozomilor))

formareacromozomilorcaentitformareacromozomilorcaentitii

vizibilelamicroscopvizibilelamicroscop

LasfrLasfrituldiviziuniicelularereituldiviziuniicelularerencepeprocesuldedecondensareancepeprocesuldedecondensarea

cromozomilor,pnalagracromozomilor,pnalagraduldefibrdecromatinduldefibrdecromatin,,

ichiarpnlafibraichiarpnlafibra3030nm,10nm,10nmnm

DEZASAMBLAREA/ASAMBLAREANUCLEOSOMILORnreplicareaADN

NucleosomiisuntNucleosomiisunt

dezasambladezasamblaipemoleculaparentalipemoleculaparental,,nfanfaabifurcaabifurcaieidereplicareieidereplicare

asamblaasamblaipemoleculelefiice,ipemoleculelefiice,nordineaanteriorprezentatnordineaanteriorprezentat

TetrameriiH3TetrameriiH3H4H4vechivechirmnasociarmnasociaicuicu

moleculaADNmoleculaADNitreccaatare,itreccaatare,fielaunafielauna

dinmoleculelenoi,fdinmoleculelenoi,fielacealaltielacealalt

DimeriiH2ADimeriiH2AH2BH2Bvechivechi

sedesprinddepesedesprinddepe

ADNADNitrecitrecntintinsolunsoluie.ie.

DereDereinutinut

Diagram of a replicated and condensed metaphase

eukaryotic chromosome.(1)

Chromatid

one of the two identical parts of the chromosome after S phase. (2)

Centromere

the point where the two chromatids touch, and where the microtubules attach.(3)

Short arm.(4)

(4) Long arm.

Human chromosomes during metaphase.

G1 1 cromozom = 1 molecul ADN = 1 cromatid Cromozom monocromatidic

S Replicare ADN = dublarea cantitii de ADN

G2 1 cromozom = 2 molecule ADN identice = 2 cromatide surori Cromozom bicromatidic

Molecula ADN este complexat cu proteine

Rolul histonelor

stabilitatea i protecia moleculelor de ADNmpachetarea moleculelor ADNStructurarea cromatinei i a cromozomilorMediaz aciunea altor proteine pe molecula ADN

proteine ptr replicarea, exprimarea ADN

Alfabet grecesc Alfabet grecesc

Se citeteLiter micLiter mareSe citeteLiter micLiter mare

niualfaksibetaomicrongamapideltarho (ro)epsilonsigmazetatauetaipsilon thetaphi (fi)iotachi (hi)kappapsilambdaomegamiu

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