DNA Damage Response Protein ASCIZ Links Base Excision Repair With Immunoglobulin Gene Conversion

Biochem Biophys Res Commun. 2008 Jun 27;371(2):225-9. doi: 10.1016/j.bbrc.2008.04.052. Epub 2008 Apr 21.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / pharmacology*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / 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

Substances

  • ATMIN protein, human
  • Alkylating Agents
  • Carrier Proteins
  • Mutagens
  • Nuclear Proteins
  • Transcription Factors
  • Methyl Methanesulfonate
  • DNA Polymerase beta