APE1- And APE2-dependent DNA breaks in immunoglobulin class switch recombination

Jeroen E.J. Guikema, Erin K. Linehan, Daisuke Tsuchimoto, Yusaku Nakabeppu, Phyllis R. Strauss, Janet Stavnezer, Carol E. Schrader

Research output: Contribution to journalArticle

108 Citations (Scopus)

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. JEM

Original languageEnglish
Pages (from-to)3017-3026
Number of pages10
JournalJournal of Experimental Medicine
Volume204
Issue number12
DOIs
Publication statusPublished - Nov 26 2007

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DNA Breaks
Immunoglobulin Isotypes
Genetic Recombination
Uracil-DNA Glycosidase
DNA-(Apurinic or Apyrimidinic Site) Lyase
Single-Stranded DNA Breaks
Deamination
Endonucleases
Cytosine
DNA

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

APE1- And APE2-dependent DNA breaks in immunoglobulin class switch recombination. / Guikema, Jeroen E.J.; Linehan, Erin K.; Tsuchimoto, Daisuke; Nakabeppu, Yusaku; Strauss, Phyllis R.; Stavnezer, Janet; Schrader, Carol E.

In: Journal of Experimental Medicine, Vol. 204, No. 12, 26.11.2007, p. 3017-3026.

Research output: Contribution to journalArticle

Guikema, Jeroen E.J. ; Linehan, Erin K. ; Tsuchimoto, Daisuke ; Nakabeppu, Yusaku ; Strauss, Phyllis R. ; Stavnezer, Janet ; Schrader, Carol E. / APE1- And APE2-dependent DNA breaks in immunoglobulin class switch recombination. In: Journal of Experimental Medicine. 2007 ; Vol. 204, No. 12. pp. 3017-3026.
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AU - Strauss, Phyllis R.

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