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Meiotic checkpoint responses to chromosome synapsis defects

AutorHerruzo, Esther; González-Arranz, Sara; San-Segundo, Pedro A.
Fecha de publicación2016
CitaciónMechanisms of Recombination Conference (2016)
ResumenMeiotic cells possess surveillance mechanisms or checkpoints that monitor critical meiotic events, such as recombination and chromosome synapsis. Defects in these processes, like those resulting from the absence of the Zip1 protein (a structural component of the synaptonemal complex), activate a meiosis-specific checkpoint network resulting in a delay or arrest of meiotic cell-cycle progression. We are studying this meiotic checkpoint pathway at different levels. Pch2 is an evolutionarily conserved AAA+ ATPase that impacts multiple aspects of meiotic chromosome metabolism and was initially discovered as a checkpoint protein required for the zip1-induced meiotic arrest in budding yeast. Interestingly, in the zip1 mutant, Pch2 is only detectable at the rDNA region (nucleolus). A special chromatin environment determined by the chromosomal distribution of Dot1-dependent histone H3K79 methylation and by the action of the Sir2 histone deacetylase contributes to Pch2¿s nucleolar confinement. We have found that the critical function of Pch2 in the zip1-induced meiotic checkpoint is to promote Mec1-dependent phosphorylation of the Hop1 checkpoint adaptor at threonine 318. In fact, overexpression of HOP1, but not that of the non-phosphorylatable hop1-T318A mutant, restores checkpoint action in zip1 pch2 cells. Pch2 checkpoint function depends on its ATPase activity and; curiously, ATP binding to Pch2, but not ATP hydrolysis, is required for Pch2 association to meiotic chromatin. In addition, we have discovered a potential phosphorylation site in Pch2 that can modulate its checkpoint activity and chromosomal localization pattern. We are also studying the meiotic functions of the H2A.Z histone variant. Among other roles, we found that H2A.Z is required for deactivation of the zip1-induced checkpoint; the zip1 htz1 double mutant shows a tight meiotic arrest. Rad51 foci accumulation, Hop1-T318 phosphorylation and Mek1 activation are not significantly increased in zip1 htz1 compared to zip1, but induction of Ndt80 and Cdc5 is severely delayed in the double mutant thus explaining the strong meiotic block. The absence of the Swe1 kinase suppresses the meiotic cell cycle arrest of zip1 htz1. These and other observations place H2A.Z in the control of downstream targets of the meiotic checkpoint pathway. Current insights into the molecular mechanisms underlying Pch2 and H2A.Z meiotic functions will be presented and discussed.
DescripciónResumen del póster presentado a la International Conference Mechanisms of Recombination, celebrada en Alicante (España) del 16 al 20 de mayo de 2016.
URIhttp://hdl.handle.net/10261/157374
Aparece en las colecciones: (IBFG) Comunicaciones congresos
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