Abstract
Maintenance of genomic integrity during antigen receptor gene rearrangements requires (1) regulated access of the V(D)J recombinase to specific loci and (2) generation of double-strand DNA breaks only after recognition of a pair of matched recombination signal sequences (RSSs). Here we recapitulate both key aspects of regulated recombinase accessibility in a cell-free system using plasmid substrates assembled into chromatin. We show that recruitment of the SWI/SNF chromatin-remodeling complex to both RSSs increases coupled cleavage by RAG1 and RAG2 proteins. SWI/SNF functions by altering local chromatin structure in the absence of RNA polymerase II-dependent transcription or histone modifications. These observations demonstrate a direct role for cis-sequence-regulated local chromatin remodeling in RAG1/2-dependent initiation of V(D)J recombination.
Original language | English (US) |
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Pages (from-to) | 641-649 |
Number of pages | 9 |
Journal | Molecular Cell |
Volume | 31 |
Issue number | 5 |
DOIs | |
State | Published - Sep 5 2008 |
Externally published | Yes |
Keywords
- DNA
ASJC Scopus subject areas
- Molecular Biology