Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes

Yamane, Arito; Resch, Wolfgang; Kuo, Nan; Kuchen, Stefan; Li, Zhiyu; Sun, Hong-wei; Robbiani, Davide F; McBride, Kevin; Nussenzweig, Michel C; Casellas, Rafael (2011). Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nature immunology, 12(1), pp. 62-9. New York, N.Y.: Nature Publishing Group 10.1038/ni.1964

Full text not available from this repository.

The cytidine deaminase AID hypermutates immunoglobulin genes but can also target oncogenes, leading to tumorigenesis. The extent of AID's promiscuity and its predilection for immunoglobulin genes are unknown. We report here that AID interacted broadly with promoter-proximal sequences associated with stalled polymerases and chromatin-activating marks. In contrast, genomic occupancy of replication protein A (RPA), an AID cofactor, was restricted to immunoglobulin genes. The recruitment of RPA to the immunoglobulin loci was facilitated by phosphorylation of AID at Ser38 and Thr140. We propose that stalled polymerases recruit AID, thereby resulting in low frequencies of hypermutation across the B cell genome. Efficient hypermutation and switch recombination required AID phosphorylation and correlated with recruitment of RPA. Our findings provide a rationale for the oncogenic role of AID in B cell malignancy.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology
UniBE Contributor:	Kuchen, Stefan
ISSN:	1529-2908
Publisher:	Nature Publishing Group
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:10
Last Modified:	05 Dec 2022 14:01
Publisher DOI:	10.1038/ni.1964
PubMed ID:	21113164
Web of Science ID:	000285465100014
URI:	https://boris.unibe.ch/id/eprint/1676 (FactScience: 203539)