About: JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks

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About: JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	Chromatin ubiquitylation flanking DNA double-strand breaks (DSBs), mediated by RNF8 and RNF168 ubiquitin ligases, orchestrates a two-branch pathway, recruiting repair factors 53BP1 or the RAP80-BRCA1 complex. We report that human demethylase JMJD1C regulates the RAP80-BRCA1 branch of this DNA-damage response (DDR) pathway. JMJD1C was stabilized by interaction with RNF8, was recruited to DSBs, and was required for local ubiquitylations and recruitment of RAP80-BRCA1 but not 53BP1. JMJD1C bound to RNF8 and MDC1, and demethylated MDC1 at Lys45, thereby promoting MDC1-RNF8 interaction, RNF8-dependent MDC1 ubiquitylation and recruitment of RAP80-BRCA1 to polyubiquitylated MDC1. Furthermore, JMJD1C restricted formation of RAD51 repair foci, and JMJD1C depletion caused resistance to ionizing radiation and PARP inhibitors, phenotypes relevant to aberrant loss of JMJD1C in subsets of breast carcinomas. These findings identify JMJD1C as a DDR component, with implications for genome-integrity maintenance, tumorigenesis and cancer treatment. Chromatin ubiquitylation flanking DNA double-strand breaks (DSBs), mediated by RNF8 and RNF168 ubiquitin ligases, orchestrates a two-branch pathway, recruiting repair factors 53BP1 or the RAP80-BRCA1 complex. We report that human demethylase JMJD1C regulates the RAP80-BRCA1 branch of this DNA-damage response (DDR) pathway. JMJD1C was stabilized by interaction with RNF8, was recruited to DSBs, and was required for local ubiquitylations and recruitment of RAP80-BRCA1 but not 53BP1. JMJD1C bound to RNF8 and MDC1, and demethylated MDC1 at Lys45, thereby promoting MDC1-RNF8 interaction, RNF8-dependent MDC1 ubiquitylation and recruitment of RAP80-BRCA1 to polyubiquitylated MDC1. Furthermore, JMJD1C restricted formation of RAD51 repair foci, and JMJD1C depletion caused resistance to ionizing radiation and PARP inhibitors, phenotypes relevant to aberrant loss of JMJD1C in subsets of breast carcinomas. These findings identify JMJD1C as a DDR component, with implications for genome-integrity maintenance, tumorigenesis and cancer treatment. (en)
Title	JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks (en)
skos:prefLabel	JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks (en)
skos:notation	RIV/61989592:15110/13:33145213!RIV14-MSM-15110___
http://linked.open...avai/predkladatel	Lékařská fakulta
http://linked.open...avai/riv/aktivita	P
http://linked.open...avai/riv/aktivity	P(ED0030/01/01)
http://linked.open...iv/cisloPeriodika	12
http://linked.open...vai/riv/dodaniDat	2014
http://linked.open...aciTvurceVysledku	Bártek, Jiří
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Palackého v Olomouci / Lékařská fakulta
http://linked.open...dnocenehoVysledku	81920
http://linked.open...ai/riv/idVysledku	RIV/61989592:15110/13:33145213
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	CELLS; RESECTION; BRCA1; RAP80; REPAIR PROTEINS; 53BP1 RECRUITMENT; HOMOLOGOUS RECOMBINATION; DAMAGE RESPONSE; UBIQUITIN E3 LIGASE; DOUBLE-STRAND BREAKS (en)
http://linked.open.../riv/klicoveSlovo	REPAIR PROTEINS 53BP1 RECRUITMENT RAP80 RESECTION UBIQUITIN E3 LIGASE CELLS BRCA1 DAMAGE RESPONSE HOMOLOGOUS RECOMBINATION DOUBLE-STRAND BREAKS
http://linked.open...odStatuVydavatele	GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV	[82A0240B5F56]
http://linked.open...i/riv/nazevZdroje	Nature Structural and Molecular Biology (print)
http://linked.open...in/vavai/riv/obor	FD
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	7 (xsd:int)
http://linked.open...vavai/riv/projekt	Biomedicine for regional development and human resources
http://linked.open...UplatneniVysledku	2013
http://linked.open...v/svazekPeriodika	20
http://linked.open...iv/tvurceVysledku	Bártek, Jiří Watanabe, K. Bartkova, J. Lukas, J. Watanabe, S. Akimov, V. Blagoev, B.
http://linked.open...ain/vavai/riv/wos	000328007600015
issn	1545-9993
number of pages	9 (xsd:int)
http://bibframe.org/vocab/doi	10.1038/nsmb.2702
http://localhost/t...ganizacniJednotka	15110

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