Dual Control of Yen1 Nuclease Activity and Cellular Localization by Cdk and Cdc14 Prevents Genome Instability
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Date
2014-04-10
Publication Type
Journal Article
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Abstract
The careful orchestration of cellular events such as DNA replication, repair, and segregation is essential for equal distribution of the duplicated genome into two daughter cells. To ensure that persistent recombination intermediates are resolved prior to cell division, the Yen1 Holliday junction resolvase is activated at anaphase. Here, we show that the master cell-cycle regulators, cyclin-dependent kinase (Cdk) and Cdc14 phosphatase, control the actions of Yen1. During S phase, Cdk-mediated phosphorylation of Yen1 promotes its nuclear exclusion and inhibits catalytic activity by reducing the efficiency of DNA binding. Later in the cell cycle, at anaphase, Cdc14 drives Yen1 dephosphorylation, leading to its nuclear relocalization and enzymatic activation. Using a constitutively activated form of Yen1, we show that uncontrolled Yen1 activity is detrimental to the cell: spatial and temporal restriction of Yen1 protects against genotoxic stress and, by avoiding competition with the noncrossover-promoting repair pathways, prevents loss of heterozygosity.
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published
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Journal / series
Volume
54 (1)
Pages / Article No.
94 - 106
Publisher
Cell Press
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Organisational unit
09457 - Matos, Joao (ehemalig) / Matos, Joao (former)
Notes
Received 29 October 2013, Revised 4 January 2014, Accepted 3 February 2014, Available online 13 March 2014, Published: March 13, 2014.