de la adn la cromozomi
DESCRIPTION
cromozomi, centromer, kinetocori, telomere, ciclu celular, replicareTRANSCRIPT
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De la ADN la cromozomiDe la ADN la cromozomi
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Prima etapă de condensare aPrima etapă de condensare a ADNADN
• Fibra nucleohistonica = Fibra nucleohistonica = fibra primara de 10 nmfibra primara de 10 nm• AlcătuitAlcătuita a din:din:
–– nucleozomi sinucleozomi si
– – porporttiunile internucleozomaleiunile internucleozomale
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NucleozomulNucleozomul
• Unitate structurală Unitate structurală constantaconstanta
• Alcătuit din: Alcătuit din:
octamerul de histone =octamerul de histone =2X(H2A + H2B + H3 +H4)2X(H2A + H2B + H3 +H4)
• In jurul lui se infăsoară ADN de In jurul lui se infăsoară ADN de
1,75X1,75X =146 pb=146 pb
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PorPorttiunile internucleozomaleiunile internucleozomale
Constiuite din ADN liber = ADN spacer sau linker (60 pb), Se asociază cu histona H1, Se formează o structură ce seamnă cu un sirag de mărgele.
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A doua etapă de condensare a A doua etapă de condensare a ADNADN
• Formarea fibrelor groase de Formarea fibrelor groase de cromatină (de 30 nm)cromatină (de 30 nm) – – fibra fibra solenoidalasolenoidala..
• Spiralizare in solenoide cu 6 Spiralizare in solenoide cu 6 nucleozomi/spiră.nucleozomi/spiră.
• Unitatea fundamentală de Unitatea fundamentală de organizare a cromatineiorganizare a cromatinei in in interfază.interfază.
• Favorizează interacFavorizează interactitiunile unile genice.genice.
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Al treilea nivel de organizare al Al treilea nivel de organizare al cromatineicromatinei• Plierea fibrei solenoidale in Plierea fibrei solenoidale in
bucle laterale bucle laterale (domenii) (domenii) • Lungimi diferite (20-100 kb).Lungimi diferite (20-100 kb).• Diametrul de 300 nm.Diametrul de 300 nm.• Buclele au situsuri de Buclele au situsuri de
legare la o armăturălegare la o armătură
centrală proteică, non centrală proteică, non histonicăhistonică
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Al treilea nivel de organizare al Al treilea nivel de organizare al cromatineicromatinei
• Fiecare buclă = unitate functională, de Fiecare buclă = unitate functională, de transcriptranscripttie si ie si replicare = domeniureplicare = domeniu
• Un domeniu este alcătuit din gene inlănUn domeniu este alcătuit din gene inlănttuiteuite fizic,fizic,• Activarea coordonată a genelor inlăntuite se face Activarea coordonată a genelor inlăntuite se face prin prin
deplicaturarea buclei (de către deplicaturarea buclei (de către diversi diversi factorifactori))• Buclele se fixează neregulat la armătura proteicăBuclele se fixează neregulat la armătura proteică• Se formează in anumite regiuni aglomerări de Se formează in anumite regiuni aglomerări de
bucle – CROMOMEREbucle – CROMOMERE
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CromozomiiCromozomii
• Compactarea suplimentară Compactarea suplimentară dădă nasterenastere cromatideicromatidei unui cromozom.unui cromozom.
• In metafază atinge cel mai In metafază atinge cel mai inalt grad de compactare.inalt grad de compactare.
• Grosime 700 nmGrosime 700 nm..
- Cel mai mic cromozom are 4,6 X107 pb, in interfază are 1,4 cm, in metafază are 2micrometri.
- Compactare de 10.000 X a moleculei de ADN.
- Necesar distributiei corecte a materialului genetic in diviziune.
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BENZILE CROMOZOMIBENZILE CROMOZOMIAALAELAE
• Benzile: reflectă Benzile: reflectă structura internă structura internă heterogenăheterogenă
• Regiuni din Regiuni din genom cu genom cu proprietăti si proprietăti si functii diferite.functii diferite.
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Centromerul “in intimitate”
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Kinetocorii
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Centromer-kinetocori
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- ADN frecvent repetitiv- TTAGGG
- protectia, replicarea si stabilizarea cz
- ADN+proteine: protectie impotriva
degradarii si fuziunii
Telomerele
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Ciclul celular
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Controlul ciclului celular
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Controlul ciclului celular
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Reglarea ciclului celular
• Activeaza repararea ADN
• Control cc prin blocarea in G1 pina la repararea daunelor
• Control segregarea cz
• Initiaza apoptoza in caz de daune ireparabile
• Induce senescenta cel
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Ce stim deja!
• Nucleotide– Adenina (A)– Timina (T)– Guanina (G)– Citozina (C)
• Legaturi de H• Dublu helix
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• Catene complementare– 3'-ATTGCCGTATGTATTGCGCT-5’
– 5'-TAACGGCATACATAACGCGA-3’
• Material ereditar transmis in descendenta• ADN ARN Proteine
Caracteristici ADN
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CCCrestere
Crestere si pregatire pt diviziuneMitoza
Unde? Cand? Cum? De ce?
Replicarea ADN
In diviziunea celulara
Faza SDuplicarea mat genetic
Asigurarea descendentei
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Enzimele replicarii
1. ADN polimerazele (5): sinteza dezoxiribonucleotidelor, catalizeaza formarea legaturilor fosfodiesterice
2. ADN-helicazele: ruperea puntilor de H
3. ADN-topoizomerazelor I si II: sectionare si despiralizarea catenelor ADN
4. Proteinele destabilizatoare: mentinerea separarii catenare
5. ARN-primaza:sinteza ARN-amorsor
6. Ribonucleaza H1:indeparteaza amorsele
7. ADN-ligaza: sudarea fragmentelor Okazaki
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5’
5’
3’
Proteine fixate pe ADN monocatenar
Initierea replicarii
ADN helicaza
ADN primaza
ADN bicatenar
ADN topoizomeraza
Furca de replicare
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Alungirea catenei directoare 5’ 3’
Catena continua(directoare)
ADN polimeraza
ADN polimeraza act in sensul 5’ 3Adauga 50 nucleotide pe sec
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Alungirea catenei intirziate 3’ 5’
Catena discontinua
Fragment Okazaki
ADN polimeraza actioneaza in sensul 5’ 3
ARN amorsor
ADN primaza
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Final
ARNaza H scoate ARN amorsor
ADN ligaza leaga tot
Corectarea erorilor de catre ADN pol
3’ 3’
5’
5’
5’
5’
ADN polimeraza
ADN ligaseARNaza H
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Duplicarea ADN
T A
C-G
G-CG-C
C-G
A-T
A-T
T-A
G-C
C-G
A-T
T-A
G-C
C-G
A-T
T-A
G-C
C-G A -
O molecula de ADN
Catena matrita
Molecula de ADN in curs de
sinteza
Molecula de ADN in curs de sinteza
C-
T-
G-
Enzime: ADN pol
Catena nou formata
A-T
T-A
G-C
C-G
A-T
T-A
G-C
C-G
A-T
T-A
G-C
C-G
A-T
T-A
G-C
C-G
2 molecule ADN fiice, identice
Nucleotide libere
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-ADN frecvent repetitiv- protectia, replicarea si
stabilizarea cz- ADN+proteine: protectie
impotriva degradarii si fuziunii
Telomerele 5'...TTAGGG TTAGGG TTAGGG
3'...AATCCC 5'
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• 1: ARN amorsor si primaza pt demarea replicarii.
• 2: incepe replicarea• 3: inlaturarea ARN amorsor lasa un gol, • 4: capatul telomeric se curbeaza in “ac de par”
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Telomeraza
• Ribonucleoproteina• Cromozomul 3• Viata embrionara• Stabilizarea
telomerelor• Activata prin
procese inflamatorii, cancer
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Telomeraza: cind si cum?
1. Segment GGGATT
2. Fragment ARN cu secventa CCCUAA
3. Telomeraza se fixeaza pe telomere
4. Sinteza ADN telomeric ce alungeste catena 3