title: DNA damage response during mouse oocyte maturation.
abstract: 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 γH2AX 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 γH2AX foci in metaphase II.  Compromised DNA integrity in mirin-treated oocytes indicates a role for MRE11 in chromosome integrity during meiotic maturation.
authors.affiliation: a Institute of Animal Physiology and Genetics AS CR , Libechov , Czech Republic.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Mayer
authors.affiliation: a Institute of Animal Physiology and Genetics AS CR , Libechov , Czech Republic.|b Institute of Animal Physiology , Kosice , Slovakia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Baran
authors.affiliation: c Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology , Kobe , Japan.
authors.forename: Yogo
authors.initials: Y
authors.lastname: Sakakibara
authors.affiliation: a Institute of Animal Physiology and Genetics AS CR , Libechov , Czech Republic.
authors.forename: Adela
authors.initials: A
authors.lastname: Brzakova
authors.affiliation: a Institute of Animal Physiology and Genetics AS CR , Libechov , Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ferencova
authors.affiliation: a Institute of Animal Physiology and Genetics AS CR , Libechov , Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Motlik
authors.affiliation: c Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology , Kobe , Japan.
authors.forename: Tomoya S
authors.initials: TS
authors.lastname: Kitajima
authors.affiliation: d Department of Biology , University of Pennsylvania , Philadelphia , PA , USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schultz
authors.affiliation: a Institute of Animal Physiology and Genetics AS CR , Libechov , Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Solc
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006657:Histones / Q000235:genetics; D000076228:MRE11 Homologue Protein; D008540:Meiosis / Q000235:genetics*; D008677:Metaphase / Q000235:genetics; D051379:Mice; D009865:Oocytes / Q000254:growth & development / Q000378:metabolism*; D009353:Zinostatin / Q000008:administration & dosage
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D006657:Histones; D000076228:MRE11 Homologue Protein; D009353:Zinostatin; C512689:Mre11a protein, mouse; C576325:Atm protein, mouse; C475961:gamma-H2AX protein, mouse
keywords: DNA damage; MRE11; double strand DNA breaks; meiotic maturation; mouse oocytes