Title

Mapping of switch recombination junctions, a tool for studying DNA repair pathways during immunoglobulin class switching

UMMS Affiliation

Department of Microbiology and Physiological Systems; Program in Immunology and Virology

Date

11-2010

Document Type

Article

Medical Subject Headings

Animals; B-Lymphocytes; *DNA Repair; Humans; *Immunoglobulin Class Switching; Immunoglobulin Isotypes; Mice

Disciplines

Genetics and Genomics | Immunology and Infectious Disease

Abstract

Class switch recombination (CSR) is induced upon B cell activation and occurs within special DNA regions, termed switch (S) regions, which consist of tandem repeats of G-rich sequences. CSR occurs by introduction of double-strand breaks (DSBs) into each S region, and recombination by nonhomologous end-joining (NHEJ). The recombination event occurs during the G1 phase of the cell cycle in cells that are rapidly dividing. By examination of patients and mouse knock-out strains lacking various DNA-damage response factors and enzymes involved in DNA repair, much has been learned about which factors are important for CSR, how DSBs are introduced into S regions, and how the donor and acceptor S regions are then recombined. One of the approaches for analyzing the steps involved in CSR is to determine the nucleotide sequence of S-S junctions. Many of the DNA repair deficiencies alter the sequence of the recombination junctions, generally increasing the use of microhomologies, interpreted as a shift from classical (C)-NHEJ to alternative end-joining (A-EJ). However, it is clear that A-EJ, is not simply one pathway; rather, recombination is likely to occur using various subsets of end-joining factors, which will vary depending on the structure of the DSBs provided by the initial phases of CSR. Herein we review the results of analyses of S-S junctions, suggest minimal information required for these analyses, and attempt to integrate these results in order to increase our understanding of the complex process of CSR.

Comments

Citation: Adv Immunol. 2010;108:45-109. doi: 10.1016/B978-0-12-380995-7.00003-3. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

21056729