Format

Send to

Choose Destination
J Exp Med. 2012 Oct 22;209(11):2099-111. doi: 10.1084/jem.20112145. Epub 2012 Sep 24.

A role for the RNA pol II-associated PAF complex in AID-induced immune diversification.

Author information

1
DNA Editing Laboratory, London Research Institute, South Mimms EN6 3LD, England, UK.

Abstract

Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated and characterized endogenous AID-containing protein complexes from the chromatin of diversifying B cells. The majority of proteins associated with AID belonged to RNA polymerase II elongation and chromatin modification complexes. Besides the two core polymerase subunits, members of the PAF complex, SUPT5H, SUPT6H, and FACT complex associated with AID. We show that AID associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain, that depletion of PAF complex members inhibits AID-induced immune diversification, and that the PAF complex can serve as a binding platform for AID on chromatin. A model is emerging of how RNA polymerase II elongation and pausing induce and resolve AID lesions.

PMID:
23008333
PMCID:
PMC3478926
DOI:
10.1084/jem.20112145
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center