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Phosphoregulation of DSB-1 mediates control of meiotic double-strand break activity.
Guo, Heyun; Stamper, Ericca L; Sato-Carlton, Aya; Shimazoe, Masa A; Li, Xuan; Zhang, Liangyu; Stevens, Lewis; Tam, K C Jacky; Dernburg, Abby F; Carlton, Peter M.
Afiliação
  • Guo H; Graduate School of Biostudies, Kyoto University, Yoshidakonoe, Sakyo, Kyoto, Japan.
  • Stamper EL; Department of Molecular and Cell Biology, University of California, Berkeley, United States.
  • Sato-Carlton A; Howard Hughes Medical Institute, Chevy Chase, United States.
  • Shimazoe MA; California Institute for Quantitative Biosciences, Berkeley, United States.
  • Li X; Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, United States.
  • Zhang L; Graduate School of Biostudies, Kyoto University, Yoshidakonoe, Sakyo, Kyoto, Japan.
  • Stevens L; Graduate School of Biostudies, Kyoto University, Yoshidakonoe, Sakyo, Kyoto, Japan.
  • Tam KCJ; Department of Science, Kyoto University, Kyoto, Japan.
  • Dernburg AF; Graduate School of Biostudies, Kyoto University, Yoshidakonoe, Sakyo, Kyoto, Japan.
  • Carlton PM; Department of Molecular and Cell Biology, University of California, Berkeley, United States.
Elife ; 112022 06 27.
Article em En | MEDLINE | ID: mdl-35758641
In the first meiotic cell division, proper segregation of chromosomes in most organisms depends on chiasmata, exchanges of continuity between homologous chromosomes that originate from the repair of programmed double-strand breaks (DSBs) catalyzed by the Spo11 endonuclease. Since DSBs can lead to irreparable damage in germ cells, while chromosomes lacking DSBs also lack chiasmata, the number of DSBs must be carefully regulated to be neither too high nor too low. Here, we show that in Caenorhabditis elegans, meiotic DSB levels are controlled by the phosphoregulation of DSB-1, a homolog of the yeast Spo11 cofactor Rec114, by the opposing activities of PP4PPH-4.1 phosphatase and ATRATL-1 kinase. Increased DSB-1 phosphorylation in pph-4.1 mutants correlates with reduction in DSB formation, while prevention of DSB-1 phosphorylation drastically increases the number of meiotic DSBs both in pph-4.1 mutants and in the wild-type background. C. elegans and its close relatives also possess a diverged paralog of DSB-1, called DSB-2, and loss of dsb-2 is known to reduce DSB formation in oocytes with increasing age. We show that the proportion of the phosphorylated, and thus inactivated, form of DSB-1 increases with age and upon loss of DSB-2, while non-phosphorylatable DSB-1 rescues the age-dependent decrease in DSBs in dsb-2 mutants. These results suggest that DSB-2 evolved in part to compensate for the inactivation of DSB-1 through phosphorylation, to maintain levels of DSBs in older animals. Our work shows that PP4PPH-4.1, ATRATL-1, and DSB-2 act in concert with DSB-1 to promote optimal DSB levels throughout the reproductive lifespan.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Saccharomyces cerevisiae / Proteínas de Caenorhabditis elegans Limite: Animals Idioma: En Revista: Elife Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Saccharomyces cerevisiae / Proteínas de Caenorhabditis elegans Limite: Animals Idioma: En Revista: Elife Ano de publicação: 2022 Tipo de documento: Article