DNA polymerases ν and θ are required for efficient immunoglobulin V gene diversification in chicken
Open Access
- 28 June 2010
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 189 (7), 1117-1127
- https://doi.org/10.1083/jcb.200912012
Abstract
The chicken DT40 B lymphocyte line diversifies its immunoglobulin (Ig) V genes through translesion DNA synthesis–dependent point mutations (Ig hypermutation) and homologous recombination (HR)–dependent Ig gene conversion. The error-prone biochemical characteristic of the A family DNA polymerases Polν and Polθ led us to explore the role of these polymerases in Ig gene diversification in DT40 cells. Disruption of both polymerases causes a significant decrease in Ig gene conversion events, although POLN−/−/POLQ−/− cells exhibit no prominent defect in HR-mediated DNA repair, as indicated by no increase in sensitivity to camptothecin. Polη has also been previously implicated in Ig gene conversion. We show that a POLH−/−/POLN−/−/POLQ−/− triple mutant displays no Ig gene conversion and reduced Ig hypermutation. Together, these data define a role for Polν and Polθ in recombination and suggest that the DNA synthesis associated with Ig gene conversion is accounted for by three specialized DNA polymerases.This publication has 67 references indexed in Scilit:
- DNA Polymerase POLN Participates in Cross-Link Repair and Homologous RecombinationMolecular and Cellular Biology, 2010
- Evidence for the Involvement of Human DNA Polymerase N in the Repair of DNA Interstrand Cross-LinksBiochemistry, 2009
- Polζ ablation in B cells impairs the germinal center reaction, class switch recombination, DNA break repair, and genome stabilityThe Journal of Experimental Medicine, 2009
- Identification of a novel REV1‐interacting motif necessary for DNA polymerase κ functionGenes to Cells, 2009
- The 9-1-1 DNA Clamp Is Required for Immunoglobulin Gene ConversionMolecular and Cellular Biology, 2008
- Reevaluation of the role of DNA polymerase θ in somatic hypermutation of immunoglobulin genesDNA Repair, 2008
- Low-fidelity DNA synthesis by human DNA polymerase thetaNucleic Acids Research, 2008
- DNA polymerase θ (POLQ) can extend from mismatches and from bases opposite a (6-4) photoproductDNA Repair, 2008
- A unique error signature for human DNA polymerase νDNA Repair, 2007
- Vertebrate POLQ and POLβ Cooperate in Base Excision Repair of Oxidative DNA DamageMolecular Cell, 2006