DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion.
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.
Oka
Hayato
H
Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-konoe, Sakyo-ku, Kyoto 606-8501, Japan.
Sakai
Wataru
W
Sonoda
Eiichiro
E
Nakamura
Jun
J
Asagoshi
Kenjiro
K
Wilson
Samuel H
SH
Kobayashi
Masahiko
M
Yamamoto
Kenichi
K
Heierhorst
Jörg
J
Takeda
Shunichi
S
Taniguchi
Yoshihito
Y
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics*; D019951:DNA Polymerase beta / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005785:Gene Conversion; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009153:Mutagens / Q000494:pharmacology; D009687:Nuclear Proteins; D013489:Suppression, Genetic; D014157:Transcription Factors
C522841:ATMIN protein, human; D000477:Alkylating Agents; D002352:Carrier Proteins; D009153:Mutagens; D009687:Nuclear Proteins; D014157:Transcription Factors; D008741:Methyl Methanesulfonate; D019951:DNA Polymerase beta