Cdk1 Restrains NHEJ through Phosphorylation of XRCC4-like Factor Xlf1

Hentges, Pierre; Waller, Helen; Reis, Clara C.; Ferreira, Miguel Godinho; Doherty, Aidan J.

Publication

Cdk1 Restrains NHEJ through Phosphorylation of XRCC4-like Factor Xlf1

2014-12-24Journal article

dc.contributor.author	Hentges, Pierre
dc.contributor.author	Waller, Helen
dc.contributor.author	Reis, Clara C.
dc.contributor.author	Ferreira, Miguel Godinho
dc.contributor.author	Doherty, Aidan J.
dc.date.accessioned	2015-10-07T16:24:17Z
dc.date.available	2015-10-07T16:24:17Z
dc.date.issued	2014-12-24
dc.description.abstract	Eukaryotic cells use two principal mechanisms for repairing DNA double-strand breaks (DSBs): homologous recombination (HR) and nonhomologous end-joining (NHEJ). DSB repair pathway choice is strongly regulated during the cell cycle. Cyclin-dependent kinase 1 (Cdk1) activates HR by phosphorylation of key recombination factors. However, a mechanism for regulating the NHEJ pathway has not been established. Here, we report that Xlf1, a fission yeast XLF ortholog, is a key regulator of NHEJ activity in the cell cycle. We show that Cdk1 phosphorylates residues in the C terminus of Xlf1 over the course of the cell cycle. Mutation of these residues leads to the loss of Cdk1 phosphorylation, resulting in elevated levels of NHEJ repair in vivo. Together, these data establish that Xlf1 phosphorylation by Cdc2(Cdk1) provides a molecular mechanism for downregulation of NHEJ in fission yeast and indicates that XLF is a key regulator of end-joining processes in eukaryotic organisms.	pt_PT
dc.description.sponsorship	Cancer Research UK Grant: (C1470/A12430), Biotechnology and Biological Sciences Research Council (BB/M004236/1), Medical Research Council (MRC; G0801130), FCT grants: (PTDC/SAU-OBD/66438/2006, PTDC/BIA-BCM/099367/2008), FCT postdoctoral fellowship, MRC-Doctoral Training Account PhD studentship, Howard Hughes Medical Institute International Early Career Scientist, Research Councils UK.	pt_PT
dc.identifier	10.1016/j.celrep.2014.11.044
dc.identifier.doi	10.1016/j.celrep.2014.11.044
dc.identifier.uri	http://hdl.handle.net/10400.7/384
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Cell Press	pt_PT
dc.relation.publisherversion	http://www.sciencedirect.com/science/article/pii/S2211124714010109	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.title	Cdk1 Restrains NHEJ through Phosphorylation of XRCC4-like Factor Xlf1	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.citation.endPage	2017	pt_PT
oaire.citation.issue	6	pt_PT
oaire.citation.startPage	2011	pt_PT
oaire.citation.title	Cell Reports	pt_PT
oaire.citation.volume	9	pt_PT
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT