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PMID: 18025127 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination.

The Journal of experimental medicine ·Vol. 204 ·No. 12 ·2007-11-26 ·Pages 3017-26

Guikema JE, Linehan EK, Tsuchimoto D, Nakabeppu Y, Strauss PR, Stavnezer J, Schrader CE

Abstract

Antibody class switch recombination (CSR) occurs by an intrachromosomal deletion requiring generation of double-stranded breaks (DSBs) in switch-region DNA. The initial steps in DSB formation have been elucidated, involving cytosine deamination by activation-induced cytidine deaminase and generation of abasic sites by uracil DNA glycosylase. However, it is not known how abasic sites are converted into single-stranded breaks and, subsequently, DSBs. Apurinic/apyrimidinic endonuclease (APE) efficiently nicks DNA at abasic sites, but it is unknown whether APE participates in CSR. We address the roles of the two major mammalian APEs, APE1 and APE2, in CSR. APE1 deficiency causes embryonic lethality in mice; we therefore examined CSR and DSBs in mice deficient in APE2 and haploinsufficient for APE1. We show that both APE1 and APE2 function in CSR, resulting in the DSBs necessary for CSR and thereby describing a novel in vivo function for APE2.

MeSH Terms
Animals B-Lymphocyte Subsets/immunology DNA Damage DNA-(Apurinic or Apyrimidinic Site) Lyase/deficiency,genetics Exodeoxyribonucleases/deficiency,genetics Gene Expression Regulation/immunology Immunoglobulin Class Switching/immunology Lymphocyte Activation Mice Mice, Knockout Recombination, Genetic Spleen/immunology
Chemicals
Exodeoxyribonucleases exodeoxyribonuclease III Apex1 protein, mouse DNA-(Apurinic or Apyrimidinic Site) Lyase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Guikema Jeroen E J
Department of Molecular Genetics and Microbiology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Linehan Erin K
Tsuchimoto Daisuke
Nakabeppu Yusaku
Strauss Phyllis R
Stavnezer Janet
Schrader Carol E
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
1540-9538
DOI
10.1084/jem.20071289
Published
2007-11-26
Epub
2007-00-19
Pages
3017-26
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118529
Subset
IM
Grants
NIAID NIH HHS · R01 AI023283 · United States
NIAID NIH HHS · R01 AI23283 · United States
NIAID NIH HHS · R01 AI63026 · United States
NIAID NIH HHS · R01 AI063026 · United States
NIAID NIH HHS · R01 AI065639 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1084/jem.20071289 PMC Full Text View journal details
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