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

Hayato Oka, Wataru Sakai, Eiichiro Sonoda, Jun Nakamura, Kenjiro Asagoshi, Samuel H. Wilson, Masahiko Kobayashi, Ken-ichi Yamamoto, Jörg Heierhorst, Shunichi Takeda, Yoshihito Taniguchi

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 polβ-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.

Original languageEnglish
Pages (from-to)225-229
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume371
Issue number2
DOIs
Publication statusPublished - Jun 27 2008
Externally publishedYes

Fingerprint

Gene Conversion
Immunoglobulin Genes
DNA Repair
DNA Damage
Methyl Methanesulfonate
Immunoglobulins
Repair
DNA
Proteins
Lymphocytes
Homologous Recombination
Chickens
Hypersensitivity
B-Lymphocytes
Substrates
link protein

Keywords

  • ASCIZ
  • ATMIN
  • Base excision repair
  • DNA polymerase β
  • DT40
  • Genetics
  • Immunoglobulin gene conversion

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion. / Oka, Hayato; Sakai, Wataru; Sonoda, Eiichiro; Nakamura, Jun; Asagoshi, Kenjiro; Wilson, Samuel H.; Kobayashi, Masahiko; Yamamoto, Ken-ichi; Heierhorst, Jörg; Takeda, Shunichi; Taniguchi, Yoshihito.

In: Biochemical and Biophysical Research Communications, Vol. 371, No. 2, 27.06.2008, p. 225-229.

Research output: Contribution to journalArticle

Oka, H, Sakai, W, Sonoda, E, Nakamura, J, Asagoshi, K, Wilson, SH, Kobayashi, M, Yamamoto, K, Heierhorst, J, Takeda, S & Taniguchi, Y 2008, 'DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion', Biochemical and Biophysical Research Communications, vol. 371, no. 2, pp. 225-229. https://doi.org/10.1016/j.bbrc.2008.04.052
Oka, Hayato ; Sakai, Wataru ; Sonoda, Eiichiro ; Nakamura, Jun ; Asagoshi, Kenjiro ; Wilson, Samuel H. ; Kobayashi, Masahiko ; Yamamoto, Ken-ichi ; Heierhorst, Jörg ; Takeda, Shunichi ; Taniguchi, Yoshihito. / DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 371, No. 2. pp. 225-229.
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