La DNA Polimerasi può commettere errori

• Nei batteri: 1 errore ogni 109 basi in ogni generazione

La correzionedelle bozze

Le basi si possono alterare spontaneamente

Correzionedelle

Bozze n2

Alterazioni del DNA indotte da agenti fisici

Alterazionida

AgentiChimici

Il DNA danneggiato

viene riparato

Due sistemi di riparazione

Le DNA polimerasi sono tante

Mammalian Cells* α β† γ δ ε

Polymerization: 5′ → 3′ + + + + +

Exonuclease proofreading activity:‡ 3 → 5′ − − + + +

Synthesis from:

     RNA primer + − − + ?

     DNA primer + + + + +

Associated DNA primase + − − − −

Sensitive to aphidicolin (inhibitor of cell DNA synthesis) + − − + +

Cell location:

     Nuclei + + − + +

     Mitochondria − − + − −

* Yeast DNA polymerase I, II, and III are equivalent to polymerase α, β, and δ, respectively. I and III are essential for cell viability.† Polymerase β is most active on DNA molecules with gaps of about 20 nucleotides and is thought to play a role in DNA repair.‡ FEN1 is the eukaryotic 5′ → 3′ exonuclease that removes RNA primers; it is similar in structure and function to the domain of E. coli polymerase I that contains the 5′ → 3′ exonuclease activity.

Malattie ereditarie legate a difetti della riparazione del DNA

Disease Sensitivity Cancer susceptibility

Complementation groups

Symptoms

Ataxiatelangiectasia

γ irradiation Lymphomas 5 Ataxia, dilation of blood vessels(telangiectases) in skin and eyes,chromosome aberrations, immunedysfunction

Bloom syndrome

Mild alkylatingagents

Carcinomas,leukemias,lymphomas

1 Photosensitivity, facial telangiectases,chromosome alterations

Cockaynesyndrome

UV light 2 Dwarfism, retinal atrophy, photosen-sitivity, progeria, deafness, trisomy 10

Fanconi anemia

Cross-linking agents Leukemias 3 Hypoplastic pancytopenia, congenitalanomalies

Xerodermapigmentosum

UV light, chemicalmutagens

Skin carcinomasand melanomas

8 Skin and eye photosensitivity, keratoses

HNPCC Colon, ovary 4 Early development of tumors

Classificazione del DNA Eucariotico

• Protein-coding genes

Solitary genes

Duplicated and diverged genes (functional gene families and nonfunctional pseudogenes)

• Tandemly repeated genes encoding rRNA, 5S rRNA,

tRNA, and histones

• Repetitious DNAModerately repeated DNA (mobile DNA elements)

• Transposons

• Viral retrotransposons

Simple-sequence DNA (Satellite DNA: eg telomeres)

Long interspersed elements (LINES; nonviral retrotransposons)

Short interspersed elements (SINES; nonviral retrotransposons)

• Unclassified spacer DNA

Classificazione del DNA Eucariotico

Genomi a Confronto

Struttura “tipo” di un Cromosoma Umano