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

Biochemical and Biophysical Research Communications
Hayato OkaYoshihito Taniguchi

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.

References

Jul 29, 2004·DNA Repair·Mitsuyoshi YamazoeShunichi Takeda
Jun 1, 2005·Nature Biotechnology·Hidetaka SeoKunihiro Ohta
Mar 3, 2007·Annual Review of Biochemistry·Javier M Di Noia, Michael S Neuberger
May 26, 2007·The EMBO Journal·Nnennaya Kanu, Axel Behrens

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Citations

Aug 15, 2012·The Journal of Experimental Medicine·Sabine JuradoJörg Heierhorst
Oct 27, 2010·PLoS Genetics·Sabine JuradoJörg Heierhorst
Aug 6, 2009·PloS One·Katsuhiko YoshizawaRobert W Sobol
Jun 27, 2015·PloS One·Shiau-Mei ChenChen-Yang Shen
Jul 10, 2019·Mutagenesis·Alanna R Kaplan, Peter M Glazer

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