Absence of Ku70 gene obliterates X-ray-induced lacZ mutagenesis of small deletions in mouse tissues

Yoshihiko Uehara, Hironobu Ikehata, Jun Ichro Komura, Ari Ito, Masaki Ogata, Tsunetoshi Itoh, Ryoichi Hirayama, Yoshiya Furusawa, Koichi Ando, Tatjana Paunesku, Gayle E. Woloschak, Kenshi Komatsu, Shinya Matsuura, Tsuyoshi Ikura, Kenji Kamiya, Tetsuya Ono*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

With the goal of understanding the role of non-homologous end-joining repair in the maintenance of genetic information at the tissue level, we studied mutations induced by radiation and subsequent repair of DNA double-strand breaks in Ku70 gene-deficient lacZ transgenic mice. The local mutation frequencies and types of mutations were analyzed on a lacZ gene that had been chromosomally integrated, which allowed us to monitor DNA sequence alterations within this 3.1-kbp region. The mutagenic process leading to the development of the most frequently observed small deletions in wild-type mice after exposure to 20 Gy of X rays was suppressed in Ku70-/- mice in the three tissues examined: spleen, liver and brain. Examination of DNA break rejoining and the phosphorylation of histone H2AX in Ku70-deficient and -proficient mice revealed that Ku70 deficiency decreased the frequency of DNA rejoining, suggesting that DNA rejoining is one of the causes of radiation-induced deletion mutations. Limited but statistically significant DNA rejoining was found in the liver and brain of Ku70-deficient mice 3.5 days after irradiation, showing the presence of a DNA double-strand break repair system other than non-homologous end joining. These data indicate a predominant role of non-homologous end joining in the production of radiation-induced mutations in vivo.

Original languageEnglish (US)
Pages (from-to)216-223
Number of pages8
JournalRadiation Research
Volume170
Issue number2
DOIs
StatePublished - Aug 2008

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Absence of Ku70 gene obliterates X-ray-induced lacZ mutagenesis of small deletions in mouse tissues'. Together they form a unique fingerprint.

Cite this