@article{2d51e3ab07ed40d385d1367f92c38150,
title = "Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis",
abstract = "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.",
keywords = "Zscan5b, chromosome instability syndrome, embryonic stem cell, genome integrity, knockout mouse, mitosis, mosaicism, postreplicative DNA damage repair",
author = "Seiji Ogawa and Mitsutoshi Yamada and Akihiro Nakamura and Tohru Sugawara and Akari Nakamura and Shoko Miyajima and Yuichirou Harada and Reina Ooka and Ryuichiro Okawa and Jun Miyauchi and Hideki Tsumura and Yasunori Yoshimura and Kenji Miyado and Hidenori Akutsu and Mamoru Tanaka and Akihiro Umezawa and Toshio Hamatani",
note = "Funding Information: We are grateful to Hideki Tsumura and the staff of the Animal Care Facility at NRICHD and Keio University for mouse husbandry, the Collaborative Research Resources of Keio University for technical support and reagents, and to Erika Suzuki and Tomoyuki Kawasaki for help with editing the figures. All authors read and approved the final manuscript. This work was supported, in part, by a National Grant-in-Aid from the Japanese Ministry of Health, Labour and Welfare ( NCCHD24-6 to T.H. and H.A.), a Grant-in-Aid from the Japan Health Sciences Foundation ( KHD1220 to T.H. and H.A.), the Kanae Foundation (to M.Y.), the Takeda Science Foundation (to M.Y.), Grants-in-Aid from the Japan Society for the Promotion of Science ( Kiban-B-25293345 and Kiban-B-16H05475 to T.H., Wakate-B-23791862 to S.O., and Wakate-A-17H05100 to M.Y.). Funding Information: We are grateful to Hideki Tsumura and the staff of the Animal Care Facility at NRICHD and Keio University for mouse husbandry, the Collaborative Research Resources of Keio University for technical support and reagents, and to Erika Suzuki and Tomoyuki Kawasaki for help with editing the figures. All authors read and approved the final manuscript. This work was supported, in part, by a National Grant-in-Aid from the Japanese Ministry of Health, Labour and Welfare (NCCHD24-6 to T.H. and H.A.), a Grant-in-Aid from the Japan Health Sciences Foundation (KHD1220 to T.H. and H.A.), the Kanae Foundation (to M.Y.), the Takeda Science Foundation (to M.Y.), Grants-in-Aid from the Japan Society for the Promotion of Science (Kiban-B-25293345 and Kiban-B-16H05475 to T.H. Wakate-B-23791862 to S.O. and Wakate-A-17H05100 to M.Y.). Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = jun,
day = "11",
doi = "10.1016/j.stemcr.2019.05.002",
language = "English",
volume = "12",
pages = "1366--1379",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "6",
}
