Mapping of switch recombination junctions, a tool for studying DNA repair pathways during immunoglobulin class switching.
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.
Department of Microbiology and Physiological Systems, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Janet
J
Stavnezer
Andrea
A
Björkman
Likun
L
Du
Alberto
A
Cagigi
Qiang
Q
Pan-Hammarström
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans; D017578:Immunoglobulin Class Switching; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D051379:Mice
D007132:Immunoglobulin Isotypes