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07. Alteraes do DNA

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Mutaes no DNA

Mutaes espontneas - replicaoMutaes induzidas: fsicas agentes que modificam as bases

qumicas UV, X-ray

Repao constante do DNA e essencial para a sobrevivncia

Sobrevivncia da clula sobrevivncia da espcie

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NAME PHENOTYPE ENZYME OR PROCESS AFFECTEDMSH2, 3, 6, MLH1, PMS2 colon cancer mismatch repair

Xeroderma pigmentosum (XP) groups AG skin cancer, cellular UV sensitivity, neurological abnormalities nucleotide excision-repairXP variant cellular UV sensitivity translesion synthesis by DNA polymerase

Ataxiatelangiectasia (AT) leukemia, lymphoma, cellular-ray sensitivity, genome instability ATM protein, a protein kinase activated by

double-strand breaks

BRCA-2 breast and ovarian cancer repair by homologous recombinationWerner syndrome premature aging, cancer at several sites, genome instability accessory 3-exonuclease and DNA helicase

Bloom syndrome cancer at several sites, stunted growth, genome instability accessory DNA helicase for replicationFanconi anemia groups AG congenital abnormalities, leukemia, genome instability DNA interstrand cross-link repair

46 BR patient hypersensitivity to DNA-damaging agents, genome instability DNA ligase I

Doenas genticas humanas associadas a reparao do DNA

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5000 bases loss every day from each cell due to spontaneous depurination

100 bases modified each day per cell by deamination to become uracil

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UV dimers

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Action of chemical on the DNA molecule

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Replication error

105 107 109

DNA polymerase Proofreading Mistmatch repear system

Fidelity of DNA replication

MRS: 1. Detects the error2. Determine which base is incorrect

3. Excise incorrect base and repair DNA

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Fixao das mutaes aps a replicao

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Fixao das mutaes aps a replicao

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Alteraes estruturais dos cromossomas: delees, inverses, traslocaes

Mutaes pontuais

- Transio troca de pir/pir ou pur/pur

- Transverso troca de pir/pur ou pur/pir

Mutaes absurdas (Nonsense)

- mutao pontual que resulta numa codo STOP

Mutaes sem sentido (missense)

- mutao pontual que altera o amino cido codificado pelo codo

Mutao silenciosa

-mutao pontual que no altera o amino cido codificado pelo codomas altera a sequencia do DNA

Mutao neutra

-mutao pontual que altera o amino cido codificado pelo codo

mas no afecta a funo da protena

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Frameshift mutations

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Uracil DNA glicosilase

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Glycosilases: flipping out the base

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2-alquilao

Cys-O6-Methylguanine (stoichiometric)

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Photolyase Prokaryotes + Eukaryotes

Very old enzyme (Bacteria to human)DNA binding domain CRY (human)

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Mistmatch DNA repair in Bacteria

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Repair by homologousrecombination

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Non-Homologous end joining

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Translesion DNA Repair

Polymerase swicth in order tocomplete DNA replication

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