title: The p53-like Protein CEP-1 Is Required for Meiotic Fidelity in C. elegans.
abstract: The passage of genetic information during meiosis requires exceptionally high fidelity to prevent birth defects and infertility. Accurate chromosome segregation during the first meiotic division relies on the formation of crossovers between homologous chromosomes and a series of precisely controlled steps to exchange genetic information. Many studies have hinted at a role for p53 in meiosis, but how it functions in this process is poorly understood. Here, we have identified a cooperative role for the p53-like protein CEP-1 and the meiotic protein HIM-5 in maintaining genome stability in the C. elegans germline. Loss of cep-1 and him-5 results in synthetic lethality that is dependent on the upstream DNA damage checkpoint but independent of the downstream core apoptotic pathway. We show that this synthetic lethality is the result of defective crossover formation due to reduced SPO-11-dependent double-strand breaks. Using cep-1 separation-of-function alleles, we show that cep-1 and him-5 also suppress inappropriate activation of the nonhomologous end joining (NHEJ) pathway. This work reveals an ancestral function for the p53 family in ensuring the fidelity of meiosis and establishes CEP-1 as a critical determinant of repair pathway choice.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors.forename: Abigail-Rachele F
authors.initials: AR
authors.lastname: Mateo
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Zebulin
authors.initials: Z
authors.lastname: Kessler
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors.forename: Anita Kristine
authors.initials: AK
authors.lastname: Jolliffe
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: McGovern
authors.affiliation: Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors.forename: Alissa
authors.initials: A
authors.lastname: Nicolucci
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address: yanowitzjl@mwri.magee.edu.
authors.forename: Judith L
authors.initials: JL
authors.lastname: Yanowitz
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada. Electronic address: brent.derry@sickkids.ca.
authors.forename: W Brent
authors.initials: WB
authors.lastname: Derry
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000502:physiology*; D008540:Meiosis / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C438244:CEP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D016159:Tumor Suppressor Protein p53