TY - JOUR
T1 - Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis
AU - Ogawa, Seiji
AU - Yamada, Mitsutoshi
AU - Nakamura, Akihiro
AU - Sugawara, Tohru
AU - Nakamura, Akari
AU - Miyajima, Shoko
AU - Harada, Yuichirou
AU - Ooka, Reina
AU - Okawa, Ryuichiro
AU - Miyauchi, Jun
AU - Tsumura, Hideki
AU - Yoshimura, Yasunori
AU - Miyado, Kenji
AU - Akutsu, Hidenori
AU - Tanaka, Mamoru
AU - Umezawa, Akihiro
AU - Hamatani, Toshio
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/6/11
Y1 - 2019/6/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stemcr.2019.05.002
DO - 10.1016/j.stemcr.2019.05.002
M3 - Article
C2 - 31155506
AN - SCOPUS:85066735191
SN - 2213-6711
VL - 12
SP - 1366
EP - 1379
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 6
ER -
