Activation of 12/23-RSS-Dependent RAG Cleavage by hSWI/SNF Complex in the Absence of Transcription

Hansen Du, Haruhiko Ishii, Michael J. Pazin, Ranjan Sen

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)641-649
Number of pages9
JournalMolecular Cell
Volume31
Issue number5
DOIs
StatePublished - Sep 5 2008
Externally publishedYes

Keywords

  • DNA

ASJC Scopus subject areas

  • Molecular Biology

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