DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion.

Abstract	ASCIZ (ATMIN) was recently identified as a novel DNA damage response protein. Here we report that ASCIZ-deficient chicken DT40 B lymphocyte lines displayed markedly increased Ig gene conversion rates, whereas overexpression of human ASCIZ reduced Ig gene conversion below wild-type levels. However, neither the efficiency of double-strand break repair nor hypermutation was affected by ASCIZ levels, indicating that ASCIZ does not directly control homologous recombination or formation of abasic sites. Loss of ASCIZ led to mild sensitivity to the base damaging agent methylmethane sulfonate (MMS), yet remarkably, suppressed the dramatic MMS hypersensitivity of polbeta-deficient cells. These data suggest that ASCIZ may affect the choice between competing base repair pathways in a manner that reduces the amount of substrates available for Ig gene conversion.
Authors	Hayato Oka, Wataru Sakai, Eiichiro Sonoda, Jun Nakamura, Kenjiro Asagoshi, Samuel H Wilson, Masahiko Kobayashi, Kenichi Yamamoto, Jörg Heierhorst, Shunichi Takeda, Yoshihito Taniguchi
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 371 Issue 2 Pg. 225-9 (Jun 27 2008) ISSN: 1090-2104 [Electronic] United States
PMID	18433721 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
Chemical References	ATMIN protein, human Alkylating Agents Carrier Proteins Mutagens Nuclear Proteins Transcription Factors Methyl Methanesulfonate DNA Polymerase beta
Topics	Alkylating Agents (pharmacology) Animals Carrier Proteins (genetics, metabolism) Cell Line DNA Damage (genetics) DNA Polymerase beta (genetics) DNA Repair (genetics) Drug Resistance (genetics) Gene Conversion Genes, Immunoglobulin (genetics) Humans Methyl Methanesulfonate (pharmacology) Mice Mice, Transgenic Mutagens (pharmacology) Nuclear Proteins Suppression, Genetic Transcription Factors

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