UMMS Affiliation

Department of Molecular Genetics and Microbiology; Program in Immunology and Virology

Publication Date

11-21-2007

Document Type

Article

Subjects

Animals; B-Lymphocyte Subsets; *DNA Damage; DNA-(Apurinic or Apyrimidinic Site) Lyase; Exodeoxyribonucleases; Gene Expression Regulation; Immunoglobulin Class Switching; Lymphocyte Activation; Mice; Mice, Knockout; Recombination, Genetic; Spleen

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: J Exp Med. 2007 Nov 26;204(12):3017-26. Epub 2007 Nov 19. Link to article on publisher's site

DOI of Published Version

10.1084/jem.20071289

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of experimental medicine

PubMed ID

18025127

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