RPA Accumulation during Class Switch Recombination Represents 5′–3′ DNA-End Resection during the S–G2/M Phase of the Cell Cycle
Activation-induced cytidine deaminase (AID) promotes chromosomal translocations by inducing DNA double-strand breaks (DSBs) at immunoglobulin (Ig) genes and oncogenes in the G1 phase. RPA is a single-stranded DNA (ssDNA)-binding protein that associates with resected DSBs in the S phase and facilita...
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2013-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712004317 |
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doaj-aaf8f984f0064196a3769b21974613df2020-11-25T01:55:15ZengElsevierCell Reports2211-12472013-01-013113814710.1016/j.celrep.2012.12.006RPA Accumulation during Class Switch Recombination Represents 5′–3′ DNA-End Resection during the S–G2/M Phase of the Cell CycleArito Yamane0Davide F. Robbiani1Wolfgang Resch2Anne Bothmer3Hirotaka Nakahashi4Thiago Oliveira5Philipp C. Rommel6Eric J. Brown7Andre Nussenzweig8Michel C. Nussenzweig9Rafael Casellas10Genomics & Immunity, NIAMS, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USAGenomics & Immunity, NIAMS, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USAGenomics & Immunity, NIAMS, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USALaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USAAbramson Family Cancer Research Institute and Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USALaboratory of Genome Integrity, NCI, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USAGenomics & Immunity, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA Activation-induced cytidine deaminase (AID) promotes chromosomal translocations by inducing DNA double-strand breaks (DSBs) at immunoglobulin (Ig) genes and oncogenes in the G1 phase. RPA is a single-stranded DNA (ssDNA)-binding protein that associates with resected DSBs in the S phase and facilitates the assembly of factors involved in homologous repair (HR), such as Rad51. Notably, RPA deposition also marks sites of AID-mediated damage, but its role in Ig gene recombination remains unclear. Here, we demonstrate that RPA associates asymmetrically with resected ssDNA in response to lesions created by AID, recombination-activating genes (RAG), or other nucleases. Small amounts of RPA are deposited at AID targets in G1 in an ATM-dependent manner. In contrast, recruitment in the S–G2/M phase is extensive, ATM independent, and associated with Rad51 accumulation. In the S–G2/M phase, RPA increases in nonhomologous-end-joining-deficient lymphocytes, where there is more extensive DNA-end resection. Thus, most RPA recruitment during class switch recombination represents salvage of unrepaired breaks by homology-based pathways during the S–G2/M phase of the cell cycle. http://www.sciencedirect.com/science/article/pii/S2211124712004317 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Arito Yamane Davide F. Robbiani Wolfgang Resch Anne Bothmer Hirotaka Nakahashi Thiago Oliveira Philipp C. Rommel Eric J. Brown Andre Nussenzweig Michel C. Nussenzweig Rafael Casellas |
| spellingShingle |
Arito Yamane Davide F. Robbiani Wolfgang Resch Anne Bothmer Hirotaka Nakahashi Thiago Oliveira Philipp C. Rommel Eric J. Brown Andre Nussenzweig Michel C. Nussenzweig Rafael Casellas RPA Accumulation during Class Switch Recombination Represents 5′–3′ DNA-End Resection during the S–G2/M Phase of the Cell Cycle Cell Reports |
| author_facet |
Arito Yamane Davide F. Robbiani Wolfgang Resch Anne Bothmer Hirotaka Nakahashi Thiago Oliveira Philipp C. Rommel Eric J. Brown Andre Nussenzweig Michel C. Nussenzweig Rafael Casellas |
| author_sort |
Arito Yamane |
| title |
RPA Accumulation during Class Switch Recombination Represents 5′–3′ DNA-End Resection during the S–G2/M Phase of the Cell Cycle |
| title_short |
RPA Accumulation during Class Switch Recombination Represents 5′–3′ DNA-End Resection during the S–G2/M Phase of the Cell Cycle |
| title_full |
RPA Accumulation during Class Switch Recombination Represents 5′–3′ DNA-End Resection during the S–G2/M Phase of the Cell Cycle |
| title_fullStr |
RPA Accumulation during Class Switch Recombination Represents 5′–3′ DNA-End Resection during the S–G2/M Phase of the Cell Cycle |
| title_full_unstemmed |
RPA Accumulation during Class Switch Recombination Represents 5′–3′ DNA-End Resection during the S–G2/M Phase of the Cell Cycle |
| title_sort |
rpa accumulation during class switch recombination represents 5′–3′ dna-end resection during the s–g2/m phase of the cell cycle |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2013-01-01 |
| description |
Activation-induced cytidine deaminase (AID) promotes chromosomal translocations by inducing DNA double-strand breaks (DSBs) at immunoglobulin (Ig) genes and oncogenes in the G1 phase. RPA is a single-stranded DNA (ssDNA)-binding protein that associates with resected DSBs in the S phase and facilitates the assembly of factors involved in homologous repair (HR), such as Rad51. Notably, RPA deposition also marks sites of AID-mediated damage, but its role in Ig gene recombination remains unclear. Here, we demonstrate that RPA associates asymmetrically with resected ssDNA in response to lesions created by AID, recombination-activating genes (RAG), or other nucleases. Small amounts of RPA are deposited at AID targets in G1 in an ATM-dependent manner. In contrast, recruitment in the S–G2/M phase is extensive, ATM independent, and associated with Rad51 accumulation. In the S–G2/M phase, RPA increases in nonhomologous-end-joining-deficient lymphocytes, where there is more extensive DNA-end resection. Thus, most RPA recruitment during class switch recombination represents salvage of unrepaired breaks by homology-based pathways during the S–G2/M phase of the cell cycle.
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| url |
http://www.sciencedirect.com/science/article/pii/S2211124712004317 |
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