Three Different Pathways Prevent Chromosome Segregation in the Presence of DNA Damage or Replication Stress in Budding Yeast

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Genetic inheritance during cell proliferation requires chromosome duplication (replication) and segregation of the replicated chromosomes to the two daughter cells. In response to the presence of DNA damage, cells block chromosome segregation to avoid the inheritance of damaged, incompletely replicated chromosomes. Failure to do so results in loss of genomic integrity. Here we show that three different, redundant pathways are responsible for such control in budding yeast, a model eukaryotic organism. One of the pathways had been described before and blocks the separation of the replicated chromosomes. We show now that two additional pathways inhibit the essential pro-mitotic Cyclin Dependent Kinase (M-CDK) activity. One of them involves the conserved inhibition of M-CDK through tyrosine phosphorylation, which was puzzlingly dispensable in the response to challenged replication in budding yeast. We show that the reason for such dispensability is the existence of redundant control of M-CDK activity by Rad53. Rad53 is part of a surveillance mechanism termed the S phase checkpoint that detects and responds to replication insults. Such control mechanism has been proposed to constitute an anti-cancer barrier in human cells.

Vyšlo v časopise: Three Different Pathways Prevent Chromosome Segregation in the Presence of DNA Damage or Replication Stress in Budding Yeast. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005468
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005468

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