Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis
| Autor: | Hidenori Akutsu, Kenji Miyado, Shoko Miyajima, Tohru Sugawara, Akari Nakamura, Yasunori Yoshimura, Jun Miyauchi, Toshio Hamatani, Seiji Ogawa, Mitsutoshi Yamada, Mamoru Tanaka, Akihiro Umezawa, Akihiro Nakamura, Hideki Tsumura, Yuichirou Harada, Ryuichiro Okawa, Reina Ooka |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
DNA repair DNA damage Kruppel-Like Transcription Factors Mitosis Biology Biochemistry Article Histones Mice 03 medical and health sciences 0302 clinical medicine Histone H1 Genetics Animals lcsh:QH301-705.5 Gene Chromosome Aberrations lcsh:R5-920 Mouse Embryonic Stem Cells Cell Biology Chromosomes Mammalian Embryonic stem cell Mice Mutant Strains Chromatin Cell biology 030104 developmental biology lcsh:Biology (General) Maternal to zygotic transition Female lcsh:Medicine (General) 030217 neurology & neurosurgery DNA Damage Developmental Biology |
| Zdroj: | Stem Cell Reports, Vol 12, Iss 6, Pp 1366-1379 (2019) |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2019.05.002 |
| Popis: | Summary: 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, genome integrity, mitosis, postreplicative DNA damage repair, embryonic stem cell, knockout mouse, chromosome instability syndrome, mosaicism |
| Databáze: | OpenAIRE |
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