NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint.

Although it has been established that nuclear factor with BRCT domain 1/ mediator of the DNA damage checkpoint protein 1 (NFBD1/MDC1) is closely involved in DNA damage response, its possible contribution to the regulation of cell- cycle progression is unclear. In the present study, we have found for...

Full description

Saved in:

Bibliographic Details
Main Authors:	Kiyohiro Ando, Toshinori Ozaki, Toru Hirota, Akira Nakagawara
Format:	article
Language:	EN
Published:	Public Library of Science (PLoS) 2013
Subjects:	Medicine R Science Q
Online Access:	https://doaj.org/article/19ab7e8f5bbf4736806f33af988247bd
Tags:	Add Tag No Tags, Be the first to tag this record!

id	oai:doaj.org-article:19ab7e8f5bbf4736806f33af988247bd
record_format	dspace
spelling	oai:doaj.org-article:19ab7e8f5bbf4736806f33af988247bd2021-11-18T08:42:24ZNFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint.1932-620310.1371/journal.pone.0082744https://doaj.org/article/19ab7e8f5bbf4736806f33af988247bd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349352/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Although it has been established that nuclear factor with BRCT domain 1/ mediator of the DNA damage checkpoint protein 1 (NFBD1/MDC1) is closely involved in DNA damage response, its possible contribution to the regulation of cell- cycle progression is unclear. In the present study, we have found for the first time that NFBD1 is phosphorylated by polo-like kinase 1 (PLK1) and has an important role in G2/M transition. Both NFBD1 and PLK1 are co-expressed in cellular nuclei throughout G2/M transition, and binding assays demonstrated direct interaction between NFBD1 and PLK1. Indeed, in vitro kinase reactions revealed that the PST domain of NFBD1 contains a potential amino acid sequence (845-DVTGEE-850) targeted by PLK1. Furthermore, enforced expression of GFP-PST but not GFP-PST(T847A) where threonine at 847 was substituted by alanine inhibited the phosphorylation levels of histone H3, suggesting a defect of M phase entry. Because PLK1 has been implicated in promoting the G2/M transition, we reasoned that overexpressed PST might serve as a pseudosubstrate for PLK1 and thus interfere with phosphorylation of endogenous PLK1 substrates. Interestingly, siRNA-mediated knockdown of NFBD1 resulted in early M phase entry and accelerated M phase progression, raising the possibility that NFBD1 is a PLK1 substrate for regulating the G2/M transition. Moreover, the constitutive active form of PLK1(T210D) overcame the ICRF-193-induced decatenation checkpoint and inhibited the interaction between NFBD1 and topoisomerase IIα, but kinase-deficient PLK1 did not. Based on these observations, we propose that PLK1-mediated phosphorylation of NFBD1 is involved in the regulation of G2/M transition by recovering a decatenation checkpoint.Kiyohiro AndoToshinori OzakiToru HirotaAkira NakagawaraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e82744 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kiyohiro Ando Toshinori Ozaki Toru Hirota Akira Nakagawara NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint.
description	Although it has been established that nuclear factor with BRCT domain 1/ mediator of the DNA damage checkpoint protein 1 (NFBD1/MDC1) is closely involved in DNA damage response, its possible contribution to the regulation of cell- cycle progression is unclear. In the present study, we have found for the first time that NFBD1 is phosphorylated by polo-like kinase 1 (PLK1) and has an important role in G2/M transition. Both NFBD1 and PLK1 are co-expressed in cellular nuclei throughout G2/M transition, and binding assays demonstrated direct interaction between NFBD1 and PLK1. Indeed, in vitro kinase reactions revealed that the PST domain of NFBD1 contains a potential amino acid sequence (845-DVTGEE-850) targeted by PLK1. Furthermore, enforced expression of GFP-PST but not GFP-PST(T847A) where threonine at 847 was substituted by alanine inhibited the phosphorylation levels of histone H3, suggesting a defect of M phase entry. Because PLK1 has been implicated in promoting the G2/M transition, we reasoned that overexpressed PST might serve as a pseudosubstrate for PLK1 and thus interfere with phosphorylation of endogenous PLK1 substrates. Interestingly, siRNA-mediated knockdown of NFBD1 resulted in early M phase entry and accelerated M phase progression, raising the possibility that NFBD1 is a PLK1 substrate for regulating the G2/M transition. Moreover, the constitutive active form of PLK1(T210D) overcame the ICRF-193-induced decatenation checkpoint and inhibited the interaction between NFBD1 and topoisomerase IIα, but kinase-deficient PLK1 did not. Based on these observations, we propose that PLK1-mediated phosphorylation of NFBD1 is involved in the regulation of G2/M transition by recovering a decatenation checkpoint.
format	article
author	Kiyohiro Ando Toshinori Ozaki Toru Hirota Akira Nakagawara
author_facet	Kiyohiro Ando Toshinori Ozaki Toru Hirota Akira Nakagawara
author_sort	Kiyohiro Ando
title	NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint.
title_short	NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint.
title_full	NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint.
title_fullStr	NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint.
title_full_unstemmed	NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint.
title_sort	nfbd1/mdc1 is phosphorylated by plk1 and controls g2/m transition through the regulation of a topoiiα-mediated decatenation checkpoint.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/19ab7e8f5bbf4736806f33af988247bd
work_keys_str_mv	AT kiyohiroando nfbd1mdc1isphosphorylatedbyplk1andcontrolsg2mtransitionthroughtheregulationofatopoiiamediateddecatenationcheckpoint AT toshinoriozaki nfbd1mdc1isphosphorylatedbyplk1andcontrolsg2mtransitionthroughtheregulationofatopoiiamediateddecatenationcheckpoint AT toruhirota nfbd1mdc1isphosphorylatedbyplk1andcontrolsg2mtransitionthroughtheregulationofatopoiiamediateddecatenationcheckpoint AT akiranakagawara nfbd1mdc1isphosphorylatedbyplk1andcontrolsg2mtransitionthroughtheregulationofatopoiiamediateddecatenationcheckpoint
_version_	1718421429682176000

NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the regulation of a TOPOIIα-mediated decatenation checkpoint.

Similar Items