RRC ID 53266
著者 Mateo AR, Kessler Z, Jolliffe AK, McGovern O, Yu B, Nicolucci A, Yanowitz JL, Derry WB.
タイトル The p53-like Protein CEP-1 Is Required for Meiotic Fidelity in C. elegans.
ジャーナル Curr Biol
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.
巻・号 26(9)
ページ 1148-58
公開日 2016-5-9
DOI 10.1016/j.cub.2016.03.036
PII S0960-9822(16)30246-9
PMID 27151662
PMC PMC5215890
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Epigenesis, Genetic Gene Expression Regulation / physiology* Meiosis / physiology* Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism*
IF 9.601
引用数 10
リソース情報
線虫 tm750