Reciprocal interaction between SIRT6 and APC/C regulates genomic stability

Abstract SIRT6 is an NAD+-dependent deacetylase that plays an important role in mitosis fidelity and genome stability. In the present study, we found that SIRT6 overexpression leads to mitosis defects and aneuploidy. We identified SIRT6 as a novel substrate of anaphase-promoting complex/cyclosome (A...

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Autores principales:	Helin Wang, Kangze Feng, Qingtao Wang, Haiteng Deng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9eb8233de787417c9a5b28961fed7a70
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spelling	oai:doaj.org-article:9eb8233de787417c9a5b28961fed7a702021-12-02T15:39:50ZReciprocal interaction between SIRT6 and APC/C regulates genomic stability10.1038/s41598-021-93684-w2045-2322https://doaj.org/article/9eb8233de787417c9a5b28961fed7a702021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93684-whttps://doaj.org/toc/2045-2322Abstract SIRT6 is an NAD+-dependent deacetylase that plays an important role in mitosis fidelity and genome stability. In the present study, we found that SIRT6 overexpression leads to mitosis defects and aneuploidy. We identified SIRT6 as a novel substrate of anaphase-promoting complex/cyclosome (APC/C), which is a master regulator of mitosis. Both CDH1 and CDC20, co-activators of APC/C, mediated SIRT6 degradation via the ubiquitination-proteasome pathway. Reciprocally, SIRT6 also deacetylated CDH1 at lysine K135 and promoted its degradation, resulting in an increase in APC/C-CDH1-targeted substrates, dysfunction in centrosome amplification, and chromosome instability. Our findings demonstrate the importance of SIRT6 for genome integrity during mitotic progression and reveal how SIRT6 and APC/C cooperate to drive mitosis.Helin WangKangze FengQingtao WangHaiteng DengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Helin Wang Kangze Feng Qingtao Wang Haiteng Deng Reciprocal interaction between SIRT6 and APC/C regulates genomic stability
description	Abstract SIRT6 is an NAD+-dependent deacetylase that plays an important role in mitosis fidelity and genome stability. In the present study, we found that SIRT6 overexpression leads to mitosis defects and aneuploidy. We identified SIRT6 as a novel substrate of anaphase-promoting complex/cyclosome (APC/C), which is a master regulator of mitosis. Both CDH1 and CDC20, co-activators of APC/C, mediated SIRT6 degradation via the ubiquitination-proteasome pathway. Reciprocally, SIRT6 also deacetylated CDH1 at lysine K135 and promoted its degradation, resulting in an increase in APC/C-CDH1-targeted substrates, dysfunction in centrosome amplification, and chromosome instability. Our findings demonstrate the importance of SIRT6 for genome integrity during mitotic progression and reveal how SIRT6 and APC/C cooperate to drive mitosis.
format	article
author	Helin Wang Kangze Feng Qingtao Wang Haiteng Deng
author_facet	Helin Wang Kangze Feng Qingtao Wang Haiteng Deng
author_sort	Helin Wang
title	Reciprocal interaction between SIRT6 and APC/C regulates genomic stability
title_short	Reciprocal interaction between SIRT6 and APC/C regulates genomic stability
title_full	Reciprocal interaction between SIRT6 and APC/C regulates genomic stability
title_fullStr	Reciprocal interaction between SIRT6 and APC/C regulates genomic stability
title_full_unstemmed	Reciprocal interaction between SIRT6 and APC/C regulates genomic stability
title_sort	reciprocal interaction between sirt6 and apc/c regulates genomic stability
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9eb8233de787417c9a5b28961fed7a70
work_keys_str_mv	AT helinwang reciprocalinteractionbetweensirt6andapccregulatesgenomicstability AT kangzefeng reciprocalinteractionbetweensirt6andapccregulatesgenomicstability AT qingtaowang reciprocalinteractionbetweensirt6andapccregulatesgenomicstability AT haitengdeng reciprocalinteractionbetweensirt6andapccregulatesgenomicstability
_version_	1718385889996963840

Reciprocal interaction between SIRT6 and APC/C regulates genomic stability

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