#translesion synthesis

Repair Pathway

DNA Pol IV and V belong to which polymerase family?

Escherichia coli DNA polymerases IV encoded by dinB and V encoded by umuD'2C belong to Y-family of translesion polymerases, distinct from canonical A-family, B-family replicases, and X-family repair enzymes. Y-family members share unique structural features including little finger domain, unusually open solvent-accessible active site that accommodates bulky lesions such as benzo[a]pyrene adducts and thymine dimers, and absence of proofreading domain. They display low processivity, synthesizing only few nucleotides per binding event. Evolutionary conservation includes human Pol eta, iota, kappa

Ref: Lehninger Principles of Biochemistry, 8th ed., Chapter 27: Y-family polymerase structural features; EMBO J 1999 Pol IV V identification

View Details

Repair Pathway

Translesion DNA synthesis is

Translesion DNA synthesis represents damage tolerance mechanism allowing replication fork to bypass bulky adducts, pyrimidine dimers, cisplatin crosslinks, or apurinic sites that block high-fidelity replicative polymerases. Specialized Y-family polymerases Pol IV and Pol V possess capacious active sites accommodating distorted base pairs but lack 3' to 5' proofreading exonuclease and exhibit relaxed Watson-Crick selection. As result, they insert nucleotides opposite lesions with high misincorporation rates, generating targeted and untargeted mutations in SOS response. Though mutagenic, TLS pre

Ref: Friedberg et al., DNA Repair and Mutagenesis, 2nd ed., Chapter 15: TLS error-prone bypass mechanism; Alberts Ch.5 SOS translesion polymerases

View Details

Replication in Prokaryotes

DNA polymerase V is part of

Severe DNA damage causes accumulation of single-stranded DNA activating RecA to stimulate autocleavage of LexA repressor derepressing over 40 SOS genes regulon. Among strongly induced are umuD and umuC genes encoding Pol V, Y-family error-prone polymerase capable of copying past pyrimidine dimers that block Pol III. Pol V requires RecA nucleoprotein filament for activation as mutasome complex. Its expression relatively late in SOS response provides last-resort translesion synthesis when excision repair incomplete enabling survival despite persisting lesions but dramatically increasing mutation

Ref: Lewin Genes XII, Chapter 16: SOS response induction of Pol V UmuC-D for translesion synthesis

View Details

Replication in Prokaryotes

DNA polymerase IV is involved in

When Pol III encounters blocking lesions like thymine dimers or apurinic sites, replication forks stall because high-fidelity active site cannot accommodate distorted template geometry. Specialized Y-family polymerases bypass damage continuing replication. Pol IV encoded by dinB gene and related Pol V are induced as part of SOS response. Pol IV performs translesion synthesis across various N2-dG adducts and alkylation lesions with lower fidelity allowing continuation at cost of increased mutagenesis. It lacks proofreading and inserts nucleotides opposite lesion where replicative enzyme cannot,

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 5: SOS and translesion polymerases Pol IV and V

View Details