title: Elevated Rad53 kinase activity influences formation and interhomolog repair of meiotic DNA double-strand breaks in budding yeast.
abstract: Meiotic cells generate physiological programmed DNA double-strand breaks (DSBs) to initiate meiotic recombination. Interhomolog repair of the programmed DSBs by meiotic recombination is vital to ensure accurate chromosome segregation at meiosis I to produce normal gametes. In budding yeast, the DNA damage checkpoint kinase Rad53 is activated by DSBs which accidentally occur as DNA lesions in mitosis and meiosis; however, meiotic programmed DSBs which occur at approximately 160 loci per genome fail to activate the kinase. Thus, Rad53 activation appears to be silenced in response to meiotic programmed DSBs. In this study, to address the biological significance of Rad53's insensitivity to meiotic DSBs, we examined the effects of Rad53 overexpression on meiotic processes. The overexpression led to partial activation of Rad53, uncovering that the negative impacts of Rad53 kinase activation on meiotic progression, and formation and interhomolog repair of meiotic programmed DSBs.
authors.affiliation: Laboratory of Genome and Chromosome Functions, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: takeusu@protein.osaka-u.ac.jp.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Usui
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kanehara
mesh_terms: D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D064447:Checkpoint Kinase 2 / Q000096:biosynthesis* / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D008540:Meiosis; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; C067022:RAD53 protein, S cerevisiae
keywords: 4′,6-diamidino-2-phenylindole; Budding yeast; CO; DAPI; DNA damage checkpoint; DNA double-strand breaks; DSBs; ISA; KD; MI; MII; Meiosis; NCO; Rad53; Recombination; TCA; UTR; crossover; in situ autophosphorylation; kinase dead; meiosis I; meiosis II; non-crossover; trichloroacetic acid; untranslated region