Work

The Strength of an Ig Switch Region Is Determined by Its Ability to Drive R Loop Formation and Its Number of WGCW Sites

Year: 2014

Type: article

Abstract: R loops exist at the murine IgH switch regions and possibly other locations, but their functional importance is unclear. In biochemical systems, R loop initiation requires DNA sequence regions containing clusters of G nucleotides, but cellular studies have not been done. Here, we vary the G-clustering, total switch region length, and the number of target sites (WGCW sites for the activation-induced deaminase) at synthetic switch regions in a murine B cell line to determine the effect on class switch recombination (CSR). G-clusters increase CSR regardless of their immediate proximity to the WGCW sites. This increase is accompanied by an increase in R loop formation. CSR efficiency correlates better with the absolute number of WGCW sites in the switch region rather than the total switch region length or density of WGCW sites. Thus, the overall strength of the switch region depends on G-clusters, which initiate R loop formation, and on the number of WGCW sites.

Source: Cell Reports

DOI: 10.1016/j.celrep.2014.06.021

Authors: Zheng Z. Zhang, Nicholas R. Pannunzio, Li Han, Chih-Lin Hsieh, Kefei Yu, Michael R. Lieber

Institutions: University of Southern California, USC Norris Comprehensive Cancer Center, Michigan State University

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $5,620