ArticlePLoS genetics2009
Genetic evidence for single-strand lesions initiating Nbs1-dependent homologous recombination in diversification of Ig v in chicken B lymphocytes.
Article in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Abasic site repair in APE1-deficient mouse embryonic stem cells: a matter for the MRN complex and ATM signaling.Nucleic acids research · 2026Article
- Monoclonal antibody generation by controlled immunoglobulin gene rearrangements.Communications biology · 2025Article
- Intermolecular Gene Conversion for the Equalization of Genome Copies in the Polyploid HaloarchaeonGenes · 2024Article
- Somatic Diversification of Rearranged Antibody Gene Segments by Intra- and Interchromosomal Templated Mutagenesis.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Mitotic recombination in yeast: what we know and what we don't know.Current opinion in genetics & development · 2021Review
- CtIP-BRCA1 complex and MRE11 maintain replication forks in the presence of chain terminating nucleoside analogs.Nucleic acids research · 2019Article
- Article
- Review
- DNA strand-exchange patterns associated with double-strand break-induced and spontaneous mitotic crossovers in Saccharomyces cerevisiae.PLoS genetics · 2018Article
- A double-strand break can trigger immunoglobulin gene conversion.Nucleic acids research · 2017Article
- Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides.Cell cycle (Georgetown, Tex.) · 2016Article
- Positive Cofactor 4 (PC4) is critical for DNA repair pathway re-routing in DT40 cells.Scientific reports · 2016Article
- Distinct genetic control of homologous recombination repair of Cas9-induced double-strand breaks, nicks and paired nicks.Nucleic acids research · 2016Article
- The role of HERC2 and RNF8 ubiquitin E3 ligases in the promotion of translesion DNA synthesis in the chicken DT40 cell line.DNA repair · 2016Article
- Mechanisms of gene targeting in higher eukaryotes.Cellular and molecular life sciences : CMLS · 2016Review
- Relative contribution of four nucleases, CtIP, Dna2, Exo1 and Mre11, to the initial step of DNA double-strand break repair by homologous recombination in both the chicken DT40 and human TK6 cell lines.Genes to cells : devoted to molecular & cellular mechanisms · 2015Article
- Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia.Science advances · 2015Article
- The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ.Nucleic acids research · 2015Article
- Article
- C-terminal region of activation-induced cytidine deaminase (AID) is required for efficient class switch recombination and gene conversion.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Homologous recombination (HR) is initiated by DNA double-strand breaks (DSB). However, it remains unclear whether single-strand lesions also initiate HR in genomic DNA. Chicken B lymphocytes diversify their Immunoglobulin (Ig) V genes through HR (Ig gene conversion) and non-templated hypermutation. Both types of Ig V diversification are initiated by AID-dependent abasic-site formation. Abasic sites stall replication, resulting in the formation of single-stranded gaps. These gaps can be filled by error-prone DNA polymerases, resulting in hypermutation. However, it is unclear whether these single-strand gaps can also initiate Ig gene conversion without being first converted to DSBs. The Mre11-Rad50-Nbs1 (MRN) complex, which produces 3' single-strand overhangs, promotes the initiation of DSB-induced HR in yeast. We show that a DT40 line expressing only a truncated form of Nbs1 (Nbs1(p70)) exhibits defective HR-dependent DSB repair, and a significant reduction in the rate--though not the fidelity--of Ig gene conversion. Interestingly, this defective gene conversion was restored to wild type levels by overproduction of Escherichia coli SbcB, a 3' to 5' single-strand-specific exonuclease, without affecting DSB repair. Conversely, overexpression of chicken Exo1 increased the efficiency of DSB-induced gene-targeting more than 10-fold, with no effect on Ig gene conversion. These results suggest that Ig gene conversion may be initiated by single-strand gaps rather than by DSBs, and, like SbcB, the MRN complex in DT40 may convert AID-induced lesions into single-strand gaps suitable for triggering HR. In summary, Ig gene conversion and hypermutation may share a common substrate-single-stranded gaps. Genetic analysis of the two types of Ig V diversification in DT40 provides a unique opportunity to gain insight into the molecular mechanisms underlying the filling of gaps that arise as a consequence of replication blocks at abasic sites, by HR and error-prone polymerases.
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