Chapter $$16$$ – DNA Repair Mechanisms

This flashcard set covers the enzymes, mechanisms, and clinical correlations of DNA repair pathways, including BER, NER, MMR, and double-strand break repair.

Photolyase

A repair enzyme present in prokaryotes but absent in humans that breaks thymine dimers by absorbing UV/blue light energy to cleave the cyclobutane ring.

MGMT ($O6-Methylguanine$-DNA Methyltransferase)

A suicide enzyme that performs direct repair by transferring methyl groups from guanine to itself; high levels are linked to chemotherapy resistance against alkylating agents.

Base Excision Repair (BER)

A highly accurate, single-base repair system used for small, non-helix-distorting damage such as oxidation or deamination.

DNA Glycosylase

An enzyme in the BER pathway that recognizes a specific damaged base (e.g., uracil) and removes it to form an AP site.

AP Endonuclease

An enzyme that cuts the phosphodiester backbone at an AP site during Base Excision Repair.

Nucleotide Excision Repair (NER)

A repair mechanism for bulky, helix-distorting lesions like UV-induced thymine dimers that involves excinuclease, helicase, DNA polymerase, and ligase.

Xeroderma Pigmentosum

An inherited autosomal recessive disorder caused by mutations in $XPA-XPG$ genes that impair NER, clinical features include extreme UV sensitivity and high skin cancer risk.

Mismatch Repair (MMR)

A system that fixes incorrect base pairing from replication errors by using methylation to distinguish the old template strand from the newly synthesized strand.

MutS

The key enzyme in the Mismatch Repair pathway responsible for detecting the base mismatch.

MutH

The enzyme in Mismatch Repair that cuts the newly synthesized DNA strand once a mismatch is identified.

Lynch Syndrome (HNPCC)

An inherited genetic condition caused by mutations in MMR genes, affecting about $1$ in $279$ people and increasing the risk of colorectal and endometrial cancers.

Homologous Recombination (HR)

A high-fidelity, template-based repair process for double-strand breaks that utilizes a sister chromatid.

RecA / RAD51

Key enzymes for Homologous Recombination; RecA is used in prokaryotes, while RAD51 is used in eukaryotes.

Non-Homologous End Joining (NHEJ)

An error-prone repair mechanism for double-strand breaks that joins DNA ends without a template, often resulting in mutations.

Ku Proteins

Enzymes that bind to the ends of broken DNA strands during the Non-Homologous End Joining process.

DNA Ligase IV

The specific ligase enzyme responsible for joining DNA ends during Non-Homologous End Joining.

$V(D)J$ recombination

An immune system process that utilizes the NHEJ pathway to join DNA segments.

SOS Repair

An emergency repair system activated when DNA damage is extensive, allowing survival at the cost of introducing mutations.

DNA Polymerase $V$

An enzyme involved in SOS Repair that performs error-prone DNA synthesis to bypass extensive damage.