DNA damage response during mouse oocyte maturation

0458917 - ÚŽFG 2017 RIV US eng J - Journal Article
Mayer, Alexandra - Baran, Vladimír - Sakakibara, Y. - Brzáková, Adéla - Ferencová, Ivana - Motlík, Jan - Kitajima, T. - Schultz, R. M. - Šolc, Petr
DNA damage response during mouse oocyte maturation.
Cell Cycle. Roč. 15, č. 4 (2016), s. 546-558. ISSN 1538-4101. E-ISSN 1551-4005
R&D Projects: GA MŠMT LH12057; GA MŠMT ED2.1.00/03.0124
Institutional support: RVO:67985904
Keywords : double strand DNA breaks * DNA damage * MRE11 * meiotic maturation * mouse oocytes
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.530, year: 2016

Because low levels of DNA double strand breaks (DSBs) appear not to activate the ATM-mediated prophase I checkpoint in full-grown oocytes, there may exist mechanisms to protect chromosome integrity during meiotic maturation. Using live imaging we demonstrate that low levels of DSBs induced by the radiomimetic drug Neocarzinostatin (NCS) increase the incidence of chromosome fragments and lagging chromosomes but do not lead to APC/C activation and anaphase onset delay. The number of DSBs, represented by gamma H2AX foci, significantly decreases between prophase I and metaphase II in both control and NCS-treated oocytes. Transient treatment with NCS increases >2-fold the number of DSBs in prophase I oocytes, but less than 30% of these oocytes enter anaphase with segregation errors. MRE11, but not ATM, is essential to detect DSBs in prophase I and is involved in H2AX phosphorylation during metaphase I. Inhibiting MRE11 by mirin during meiotic maturation results in anaphase bridges and also increases the number of gamma H2AX foci in metaphase II. Compromised DNA integrity in mirin-treated oocytes indicates a role for MRE11 in chromosome integrity during meiotic maturation.
Permanent Link: http://hdl.handle.net/11104/0259129