A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei.

A-type lamins encoded by LMNA form a structural fibrillar meshwork within the mammalian nucleus. How this nuclear organization may influence the execution of biological processes involving DNA transactions remains unclear. Here, we characterize changes in the dynamics and biochemical interactions of...

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Autores principales:	Robert Mahen, Hiroyoshi Hattori, Miyoung Lee, Pooja Sharma, Anand D Jeyasekharan, Ashok R Venkitaraman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/225051a2dcf14674bf60a5ee05576b81
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spelling	oai:doaj.org-article:225051a2dcf14674bf60a5ee05576b812021-11-18T07:47:05ZA-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei.1932-620310.1371/journal.pone.0061893https://doaj.org/article/225051a2dcf14674bf60a5ee05576b812013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23658700/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203A-type lamins encoded by LMNA form a structural fibrillar meshwork within the mammalian nucleus. How this nuclear organization may influence the execution of biological processes involving DNA transactions remains unclear. Here, we characterize changes in the dynamics and biochemical interactions of lamin A/C after DNA damage. We find that DNA breakage reduces the mobility of nucleoplasmic GFP-lamin A throughout the nucleus as measured by dynamic fluorescence imaging and spectroscopy in living cells, suggestive of incorporation into stable macromolecular complexes, but does not induce the focal accumulation of GFP-lamin A at damage sites. Using a proximity ligation assay and biochemical analyses, we show that lamin A engages chromatin via histone H2AX and its phosphorylated form (γH2AX) induced by DNA damage, and that these interactions are enhanced after DNA damage. Finally, we use three-dimensional time-lapse imaging to show that LMNA inactivation significantly reduces the positional stability of DNA repair foci in living cells. This defect is partially rescued by the stable expression of GFP-lamin A. Thus collectively, our findings suggest that the dynamic structural meshwork formed by A-type lamins anchors sites of DNA repair in mammalian nuclei, providing fresh insight into the control of DNA transactions by nuclear structural organization.Robert MahenHiroyoshi HattoriMiyoung LeePooja SharmaAnand D JeyasekharanAshok R VenkitaramanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e61893 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robert Mahen Hiroyoshi Hattori Miyoung Lee Pooja Sharma Anand D Jeyasekharan Ashok R Venkitaraman A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei.
description	A-type lamins encoded by LMNA form a structural fibrillar meshwork within the mammalian nucleus. How this nuclear organization may influence the execution of biological processes involving DNA transactions remains unclear. Here, we characterize changes in the dynamics and biochemical interactions of lamin A/C after DNA damage. We find that DNA breakage reduces the mobility of nucleoplasmic GFP-lamin A throughout the nucleus as measured by dynamic fluorescence imaging and spectroscopy in living cells, suggestive of incorporation into stable macromolecular complexes, but does not induce the focal accumulation of GFP-lamin A at damage sites. Using a proximity ligation assay and biochemical analyses, we show that lamin A engages chromatin via histone H2AX and its phosphorylated form (γH2AX) induced by DNA damage, and that these interactions are enhanced after DNA damage. Finally, we use three-dimensional time-lapse imaging to show that LMNA inactivation significantly reduces the positional stability of DNA repair foci in living cells. This defect is partially rescued by the stable expression of GFP-lamin A. Thus collectively, our findings suggest that the dynamic structural meshwork formed by A-type lamins anchors sites of DNA repair in mammalian nuclei, providing fresh insight into the control of DNA transactions by nuclear structural organization.
format	article
author	Robert Mahen Hiroyoshi Hattori Miyoung Lee Pooja Sharma Anand D Jeyasekharan Ashok R Venkitaraman
author_facet	Robert Mahen Hiroyoshi Hattori Miyoung Lee Pooja Sharma Anand D Jeyasekharan Ashok R Venkitaraman
author_sort	Robert Mahen
title	A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei.
title_short	A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei.
title_full	A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei.
title_fullStr	A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei.
title_full_unstemmed	A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei.
title_sort	a-type lamins maintain the positional stability of dna damage repair foci in mammalian nuclei.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/225051a2dcf14674bf60a5ee05576b81
work_keys_str_mv	AT robertmahen atypelaminsmaintainthepositionalstabilityofdnadamagerepairfociinmammaliannuclei AT hiroyoshihattori atypelaminsmaintainthepositionalstabilityofdnadamagerepairfociinmammaliannuclei AT miyounglee atypelaminsmaintainthepositionalstabilityofdnadamagerepairfociinmammaliannuclei AT poojasharma atypelaminsmaintainthepositionalstabilityofdnadamagerepairfociinmammaliannuclei AT ananddjeyasekharan atypelaminsmaintainthepositionalstabilityofdnadamagerepairfociinmammaliannuclei AT ashokrvenkitaraman atypelaminsmaintainthepositionalstabilityofdnadamagerepairfociinmammaliannuclei
_version_	1718422959721283584

A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei.

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