ArticlePLoS biology2010
The BRCT domain of PARP-1 is required for immunoglobulin gene conversion.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- The role of autophagy in spinal cord injury: Mechanisms, crosstalk, and therapeutic strategies.Neural regeneration research · 2026Article
- BRCT Domains: Structure, Functions, and Implications in Disease-New Therapeutic Targets for Innovative Drug Discovery against Infections.Pharmaceutics · 2023Review
- TET3 dioxygenase modulates gene conversion at the avian immunoglobulin variable region via demethylation of non-CpG sites in pseudogene templates.Genes to cells : devoted to molecular & cellular mechanisms · 2021Article
- Restriction of AID activity and somatic hypermutation by PARP-1.Nucleic acids research · 2019Article
- SUMOylation of PCNA by PIAS1 and PIAS4 promotes template switch in the chicken and human B cell lines.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Review
- Correction: The BRCT Domain of PARP-1 Is Required for Immunoglobulin Gene Conversion.PLoS biology · 2018Article
- Asthma and poly(ADP-ribose) polymerase inhibition: a new therapeutic approach.Drug design, development and therapy · 2018Review
- Expression of MLL-AF4 or AF4-MLL fusions does not impact the efficiency of DNA damage repair.Oncotarget · 2016Article
- PARP activation promotes nuclear AID accumulation in lymphoma cells.Oncotarget · 2016Article
- Sirtuins in stress response: guardians of the genome.Oncogene · 2014Review
- Review
- Poly(ADP-ribose) polymerase 1 is a key regulator of estrogen receptor α-dependent gene transcription.The Journal of biological chemistry · 2013Article
- BCL2 suppresses PARP1 function and nonapoptotic cell death.Cancer research · 2012Article
- SIRT6 promotes DNA repair under stress by activating PARP1.Science (New York, N.Y.) · 2011Article
- Competition between PARP-1 and Ku70 control the decision between high-fidelity and mutagenic DNA repair.DNA repair · 2011Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Genetic variation at immunoglobulin (Ig) gene variable regions in B-cells is created through a multi-step process involving deamination of cytosine bases by activation-induced cytidine deaminase (AID) and their subsequent mutagenic repair. To protect the genome from dangerous, potentially oncogenic effects of off-target mutations, both AID activity and mutagenic repair are targeted specifically to the Ig genes. However, the mechanisms of targeting are unknown and recent data have highlighted the role of regulating mutagenic repair to limit the accumulation of somatic mutations resulting from the more widely distributed AID-induced lesions to the Ig genes. Here we investigated the role of the DNA damage sensor poly-(ADPribose)-polymerase-1 (PARP-1) in the repair of AID-induced DNA lesions. We show through sequencing of the diversifying Ig genes in PARP-1(-/-) DT40 B-cells that PARP-1 deficiency results in a marked reduction in gene conversion events and enhanced high-fidelity repair of AID-induced lesions at both Ig heavy and light chains. To further characterize the role of PARP-1 in the mutagenic repair of AID-induced lesions, we performed functional analyses comparing the role of engineered PARP-1 variants in high-fidelity repair of DNA damage induced by methyl methane sulfonate (MMS) and the mutagenic repair of lesions at the Ig genes induced by AID. This revealed a requirement for the previously uncharacterized BRCT domain of PARP-1 to reconstitute both gene conversion and a normal rate of somatic mutation at Ig genes, while being dispensable for the high-fidelity base excision repair. From these data we conclude that the BRCT domain of PARP-1 is required to initiate a significant proportion of the mutagenic repair specific to diversifying antibody genes. This role is distinct from the known roles of PARP-1 in high-fidelity DNA repair, suggesting that the PARP-1 BRCT domain has a specialized role in assembling mutagenic DNA repair complexes involved in antibody diversification.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.