Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis

Seiji Ogawa, Mitsutoshi Yamada, Akihiro Nakamura, Tohru Sugawara, Akari Nakamura, Shoko Miyajima, Yuichirou Harada, Reina Ooka, Ryuichiro Okawa, Jun Miyauchi, Hideki Tsumura, Yasunori Yoshimura, Kenji Miyado, Hidenori Akutsu, Mamoru Tanaka, Akihiro Umezawa, Toshio Hamatani

研究成果: Article

抜粋

Zygotic genome activation (ZGA) begins after fertilization and is essential for establishing pluripotency and genome stability. However, it is unclear how ZGA genes prevent mitotic errors. Here we show that knockout of the ZGA gene Zscan5b, which encodes a SCAN domain with C2H2 zinc fingers, causes a high incidence of chromosomal abnormalities in embryonic stem cells (ESCs), and leads to the development of early-stage cancers. After irradiation, Zscan5b-deficient ESCs displayed significantly increased levels of γ-H2AX despite increased expression of the DNA repair genes Rad51l3 and Bard. Re-expression of Zscan5b reduced γ-H2AX content, implying a role for Zscan5b in DNA damage repair processes. A co-immunoprecipitation analysis showed that Zscan5b bound to the linker histone H1, suggesting that Zscan5b may protect chromosomal architecture. Our report demonstrates that the ZGA gene Zscan5b is involved in genomic integrity and acts to promote DNA damage repair and regulate chromatin dynamics during mitosis. In this article, Yamada and colleagues show that Zscan5b deficiency increases DNA stress, compromises chromosomal structure during mitosis, and leads to the development of early-stage cancers. Zscan5b deficiency may offer a murine model of human chromosomal breakage syndromes.

元の言語English
ページ(範囲)1366-1379
ページ数14
ジャーナルStem cell reports
12
発行部数6
DOI
出版物ステータスPublished - 2019 6 11

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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    Ogawa, S., Yamada, M., Nakamura, A., Sugawara, T., Nakamura, A., Miyajima, S., Harada, Y., Ooka, R., Okawa, R., Miyauchi, J., Tsumura, H., Yoshimura, Y., Miyado, K., Akutsu, H., Tanaka, M., Umezawa, A., & Hamatani, T. (2019). Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis. Stem cell reports, 12(6), 1366-1379. https://doi.org/10.1016/j.stemcr.2019.05.002