Genomics

Dataset Information

297

RPA accumulation during class switch recombination represents 5'-3' DNA end resection during the S-G2/M phase of the cell cycle


ABSTRACT: AID promotes chromosomal translocations by inducing DNA double-strand breaks (DSBs) at immunoglobulin (Ig) genes and oncogenes in G1. RPA is a 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, RAG, or other nucleases. Small amounts of RPA are deposited at AID targets in G1 in an ATM-dependent manner. In contrast, recruitment in S-G2/M is extensive, ATM-independent, and associated with Rad51 accumulation. RPA in S-G2/M increases in NHEJ-deficient lymphocytes, where there is more extensive DNA-end resection. Thus, most RPA recruitment during CSR represents salvage of un-repaired breaks by homology-based pathways during the S-G2/M phases of the cell cycle. Chip-Seq of RPA from mouse activated B cells (n = 40), mouse thymocytes (n = 6), and MEFs (n = 1). Different genotypes and/or inhibitors were used.

ORGANISM(S): Mus musculus  

SUBMITTER: Thiago Oliveira   Anne Bothmer  Eric J Brown  Rafael Casellas  Wolfgang Resch  Philipp C Rommel  Arito Yamane  Davide F Robbiani  Hirotaka Nakahashi  Andre Nussenzweig  Michel C Nussenzweig 

PROVIDER: E-GEOD-42451 | ArrayExpress | 2013-01-02

SECONDARY ACCESSION(S): GSE42451SRP017275PRJNA182307

REPOSITORIES: GEO, ArrayExpress, ENA

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