Controlling the response to DNA damage by the APC/C-Cdh1

Proper cell cycle progression is safeguarded by the oscillating activities of cyclin/cyclin-dependent kinase complexes. An important player in the regulation of mitotic cyclins is the anaphase-promoting complex/cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase. Prior to entry into mitosis, the...

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Main Authors:	de Boer, H. Rudolf, Guerrero Llobet, S., van Vugt, Marcel A. T. M.
Format:	Online
Language:	English
Published:	Springer International Publishing 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744251/

id	pubmed-4744251
recordtype	oai_dc
spelling	pubmed-47442512016-02-16 Controlling the response to DNA damage by the APC/C-Cdh1 de Boer, H. Rudolf Guerrero Llobet, S. van Vugt, Marcel A. T. M. Review Proper cell cycle progression is safeguarded by the oscillating activities of cyclin/cyclin-dependent kinase complexes. An important player in the regulation of mitotic cyclins is the anaphase-promoting complex/cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase. Prior to entry into mitosis, the APC/C remains inactive, which allows the accumulation of mitotic regulators. APC/C activation requires binding to either the Cdc20 or Cdh1 adaptor protein, which sequentially bind the APC/C and facilitate targeting of multiple mitotic regulators for proteasomal destruction, including Securin and Cyclin B, to ensure proper chromosome segregation and mitotic exit. Emerging data have indicated that the APC/C, particularly in association with Cdh1, also functions prior to mitotic entry. Specifically, the APC/C-Cdh1 is activated in response to DNA damage in G2 phase cells. These observations are in line with in vitro and in vivo genetic studies, in which cells lacking Cdh1 expression display various defects, including impaired DNA repair and aberrant cell cycle checkpoints. In this review, we summarize the current literature on APC/C regulation in response to DNA damage, the functions of APC/C-Cdh1 activation upon DNA damage, and speculate how APC/C-Cdh1 can control cell fate in the context of persistent DNA damage. Springer International Publishing 2015-12-09 2016 /pmc/articles/PMC4744251/ /pubmed/26650195 http://dx.doi.org/10.1007/s00018-015-2096-7 Text en © The author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	de Boer, H. Rudolf Guerrero Llobet, S. van Vugt, Marcel A. T. M.
spellingShingle	de Boer, H. Rudolf Guerrero Llobet, S. van Vugt, Marcel A. T. M. Controlling the response to DNA damage by the APC/C-Cdh1
author_facet	de Boer, H. Rudolf Guerrero Llobet, S. van Vugt, Marcel A. T. M.
author_sort	de Boer, H. Rudolf
title	Controlling the response to DNA damage by the APC/C-Cdh1
title_short	Controlling the response to DNA damage by the APC/C-Cdh1
title_full	Controlling the response to DNA damage by the APC/C-Cdh1
title_fullStr	Controlling the response to DNA damage by the APC/C-Cdh1
title_full_unstemmed	Controlling the response to DNA damage by the APC/C-Cdh1
title_sort	controlling the response to dna damage by the apc/c-cdh1
description	Proper cell cycle progression is safeguarded by the oscillating activities of cyclin/cyclin-dependent kinase complexes. An important player in the regulation of mitotic cyclins is the anaphase-promoting complex/cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase. Prior to entry into mitosis, the APC/C remains inactive, which allows the accumulation of mitotic regulators. APC/C activation requires binding to either the Cdc20 or Cdh1 adaptor protein, which sequentially bind the APC/C and facilitate targeting of multiple mitotic regulators for proteasomal destruction, including Securin and Cyclin B, to ensure proper chromosome segregation and mitotic exit. Emerging data have indicated that the APC/C, particularly in association with Cdh1, also functions prior to mitotic entry. Specifically, the APC/C-Cdh1 is activated in response to DNA damage in G2 phase cells. These observations are in line with in vitro and in vivo genetic studies, in which cells lacking Cdh1 expression display various defects, including impaired DNA repair and aberrant cell cycle checkpoints. In this review, we summarize the current literature on APC/C regulation in response to DNA damage, the functions of APC/C-Cdh1 activation upon DNA damage, and speculate how APC/C-Cdh1 can control cell fate in the context of persistent DNA damage.
publisher	Springer International Publishing
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744251/
_version_	1613534900445511680

Controlling the response to DNA damage by the APC/C-Cdh1

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