Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 275, Issue 31, Pages 24163-24172Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M003343200
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- NIAID NIH HHS [AI-31531] Funding Source: Medline
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Immunoglobulin (Tg) heavy chain class switch recombination (CSR) mediates isotype switching during B cell development. CSR occurs between switch (S) regions that precede each Ig heavy chain constant region gene. Various studies have demonstrated that transcription plays an essential role in CSR in vivo. In this study, we show that in vitro transcription of S regions in their physiological orientation induces the formation of stable R loops. Furthermore, we show that the nucleotide excision repair nucleases XPF-ERCC1 and XPG can cleave the R loops formed in the S regions. Based on these findings, we propose that CSR is initiated via a mechanism that involves transcription-dependent S region cleavage by DNA structure-specific endonucleases that function in general DNA repair processes. Such a mechanism also may underlie transcription-dependent mutagenic processes such as somatic hypermutation, and contribute to genomic instability in general.
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