DNA Damage and Repair Flashcards

Flashcards covering DNA damage and repair mechanisms discussed in the lecture notes.

Direct Repair

A process that directly modifies bases but are inactivated such as alkyltransferases.

Base Alkylation

Occurs upon exposure of DNA to alkylating agents leading to modified bases that block DNA replication or introduce mutations.

O6-methylguanine alkyltransferase (AGT or MGMT)

An enzyme that transfers a methyl group from O6-methylguanine to a cysteine residue in the enzyme active site. It can only do this once, as having become alkylated, it cannot remove the alkyl group.

Thymine dimers

Formed as photoproducts after DNA exposure to UV light; significantly distort the duplex DNA structure, causing a 30° bend.

Nucleotide Excision Repair (NER)

Two types: Global Genome (GG-NER) and Transcription Coupled (TC-NER); involves excision of phosphodiester bonds either side of a DNA lesion, followed by new DNA synthesis of replacement DNA.

Double stranded break (dsBR) repair by Homologous Recombination

Repairs DNA double strand breaks ONLY during S or G2 phase of cell cycle; uses regions of duplicated DNA homologous to ssDNA generated at breakage sites to function as template for DNA synthesis.

Double Stranded Break Repair

Functions through 2 mechanisms: Homologous recombination (HR) & Non-homologous end joining (NHEJ)

Non-homologous end joining (NEHJ)

In non-homologous end joining broken ends of the double strand break aligned, its frayed ends trimmed and/or filled in, and their strands ligated.

Base Excision Repair (BER)

Type of DNA damage repaired by Base Excision Repair; Includes Depurination, Deamination, Base oxidation & Single-strand break

DNA Damage: Oxidation of Guanine

modification of guanine to 8-oxoguanine, leading to base pairing with A, resulting in G to T and C to A substitutions in the genome

DNA Damage: Depurination

Hydrolytic cleavage of the glycosidic bond of purine deoxyribonucleosides, leads to AP site formation; Disrupts DNA double helix structure

DNA Damage: Deamination

Hydrolysis of cytosine into uracil, can also happen “by accident”; DNA polymerase is happy to accept dUTP as a substrate; leads to presence of deoxyuracil in DNA; leads to mutation due to ability of U to pair with A

Repair of Uracil in DNA by BER

Corrects small base lesions that do not significantly distort the DNA helix structure; enzymes cleaves glycosidic bond between uracil base and the ribose sugar.

Mismatch repair (MMR)

Scans newly replicated DNA for mismatches.

Mismatch Base pairing

A lesion or non-Watson–Crick base pair arises through replication errors or other mechanisms