Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin.

In Saccharomyces cerevisiae, the conserved phosphatase Cdc14 is required for the exit from mitosis. It is anchored on nucleolar chromatin by the Cfi1/Net1 protein until early anaphase, at which time it is released into the nucleoplasm. Two poorly understood, redundant pathways promote Cdc14 release,...

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Main Authors: William W Hwang, Hiten D Madhani
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-08-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC2716543?pdf=render
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author William W Hwang
Hiten D Madhani
author_facet William W Hwang
Hiten D Madhani
author_sort William W Hwang
collection DOAJ
description In Saccharomyces cerevisiae, the conserved phosphatase Cdc14 is required for the exit from mitosis. It is anchored on nucleolar chromatin by the Cfi1/Net1 protein until early anaphase, at which time it is released into the nucleoplasm. Two poorly understood, redundant pathways promote Cdc14 release, the FEAR (Cdc fourteen early release) network and the MEN (mitotic exit network). Through the analysis of genetic interactions, we report here a novel requirement for the ubiquitination of histone H2B by the Bre1 ubiquitin ligase in the cell cycle-dependent release of Cdc14 from nucleolar chromatin when the MEN is inactivated. This function for H2B ubiquitination is mediated by its activation of histone H3 methylation on lysines 4 and 79 (meH3K4 and meH3K79) but, surprisingly, is not dependent on the histone deacetylase (HDAC) Sir2, which associates with Cdc14 on nucleolar chromatin as part of the RENT complex. We also observed a defect in Cdc14 release in cells lacking H3 lysine 36 methylation (meH3K36) and in cells lacking an HDAC recruited by this modification. These histone modifications represent previously unappreciated factors required for the accessibility to and/or action on nucleolar chromatin of FEAR network components. The nonredundant role for these modifications in this context contrasts with the notion of a highly combinatorial code by which histone marks act to control biological processes.
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spelling doaj.art-4e9a01f19d714525a52950367a90dac12022-12-22T03:16:01ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042009-08-0158e100058810.1371/journal.pgen.1000588Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin.William W HwangHiten D MadhaniIn Saccharomyces cerevisiae, the conserved phosphatase Cdc14 is required for the exit from mitosis. It is anchored on nucleolar chromatin by the Cfi1/Net1 protein until early anaphase, at which time it is released into the nucleoplasm. Two poorly understood, redundant pathways promote Cdc14 release, the FEAR (Cdc fourteen early release) network and the MEN (mitotic exit network). Through the analysis of genetic interactions, we report here a novel requirement for the ubiquitination of histone H2B by the Bre1 ubiquitin ligase in the cell cycle-dependent release of Cdc14 from nucleolar chromatin when the MEN is inactivated. This function for H2B ubiquitination is mediated by its activation of histone H3 methylation on lysines 4 and 79 (meH3K4 and meH3K79) but, surprisingly, is not dependent on the histone deacetylase (HDAC) Sir2, which associates with Cdc14 on nucleolar chromatin as part of the RENT complex. We also observed a defect in Cdc14 release in cells lacking H3 lysine 36 methylation (meH3K36) and in cells lacking an HDAC recruited by this modification. These histone modifications represent previously unappreciated factors required for the accessibility to and/or action on nucleolar chromatin of FEAR network components. The nonredundant role for these modifications in this context contrasts with the notion of a highly combinatorial code by which histone marks act to control biological processes.http://europepmc.org/articles/PMC2716543?pdf=render
spellingShingle William W Hwang
Hiten D Madhani
Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin.
PLoS Genetics
title Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin.
title_full Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin.
title_fullStr Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin.
title_full_unstemmed Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin.
title_short Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin.
title_sort nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator cdc14 from nucleolar chromatin
url http://europepmc.org/articles/PMC2716543?pdf=render
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AT hitendmadhani nonredundantrequirementformultiplehistonemodificationsfortheearlyanaphasereleaseofthemitoticexitregulatorcdc14fromnucleolarchromatin