DNA Damage and Repair Flashcards

Flashcards about DNA Damage and Repair

List three sources of DNA Damage:

Radiation, Environmental chemicals, Endogenous reagents

What enzyme is involved in base alkylation during direct repair of DNA damage?

O6-methylguanine alkyltransferase (AGT or MGMT)

What is the function of MGMT?

Transfers a methyl group from O6-methylguanine to a cysteine residue in its active site, inactivating the enzyme after a single use.

What is a common modification during Base Alkylation?

Guanine to O6 -methylguanine, involving addition of methyl group to the guanine base

What are Thymine Dimers?

Formed by UV light exposure, creating intrastrand dimers (cyclobutane dimer or 6-4 photoproduct)

What are the two types of Nucleotide Excision Repair (NER)?

Global Genome (GG-NER) and Transcription Coupled (TC-NER)

What is the NER process?

Recognition of distorted DNA by XPC-RAD23B, recruitment of TFIIH, XPA, RPA, and endonucleases XPF and XPG to make incisions, DNA polymerase initiates repair synthesis, and DNA ligase seals the remaining nick.

What does Base Excision Repair (BER) do?

Repairs smaller lesions like depurination, deamination, base oxidation, and single-strand breaks.

What enzymes are involved in BER?

DNA glycosylases

What is the result of guanine modification in BER?

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

What leads to the formation of an apurinic (AP) site?

Hydrolytic cleavage of the glycosidic bond of purine deoxyribonucleosides

What leads to mutation due to ability of U to pair with A?

Hydrolysis of cytosine into uracil

What does Mismatch Repair (MMR) do?

Corrects non-Watson-Crick base pairing mismatches that occur during DNA replication.

How does MMR work in E. coli?

MutS binds to the mismatch, MutH and MutL are recruited, and the system identifies the new strand by its lack of methylation.

What are the two types of Double-Strand Break Repair (dsBR)?

Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ)

When does Homologous Recombination (HR) occur?

Occurs during S or G2 phase, using a homologous chromosome as a template.

What is involved in HR?

Involves MRN complex, Replication protein A, RAD51, and BRCA2 to invade and synthesize DNA at the break site.

What is involved in Non-Homologous End Joining (NHEJ)?

Involves Ku70/80 heterodimer binding to broken ends, attracting DNA-PK, and ligating the ends.

What is a possible result of NHEJ?

Can result in loss of nucleotides during the process.