Linked Life Data

21138837

Source:http://linkedlifedata.com/resource/pubmed/id/21138837

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-2-14
pubmed:abstractText
The essential and evolutionarily conserved Smc5-Smc6 complex (Smc5/6) is critical for the maintenance of genome stability. Partial loss of Smc5/6 function yields several defects in DNA repair, which are rescued by inactivation of the homologous recombination (HR) machinery. Thus HR is thought to be toxic to cells with defective Smc5/6. Recent work has highlighted a role for Smc5/6 and the Sgs1 DNA helicase in preventing the accumulation of unresolved HR intermediates. Here we investigate how deletion of MPH1, encoding the orthologue of the human FANCM DNA helicase, rescues the DNA damage sensitivity of smc5/6 but not sgs1? mutants. We find that MPH1 deletion diminishes accumulation of HR intermediates within both smc5/6 and sgs1? cells, suggesting that MPH1 deletion is sufficient to decrease the use of template switch recombination (TSR) to bypass DNA lesions. We further explain how avoidance of TSR is nonetheless insufficient to rescue defects in sgs1? mutants, by demonstrating a requirement for Sgs1, along with the post-replicative repair (PRR) and HR machinery, in a pathway that operates in mph1? mutants. In addition, we map the region of Mph1 that binds Smc5, and describe a novel allele of MPH1 encoding a protein unable to bind Smc5 (mph1-?60). Remarkably, mph1-?60 supports normal growth and responses to DNA damaging agents, indicating that Smc5/6 does not simply restrain the recombinogenic activity of Mph1 via direct binding. These data as a whole highlight a role for Smc5/6 and Sgs1 in the resolution of Mph1-dependent HR intermediates.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DEAD-box RNA Helicases, http://linkedlifedata.com/resource/pubmed/chemical/DNA Helicases, http://linkedlifedata.com/resource/pubmed/chemical/FANCM protein, human, http://linkedlifedata.com/resource/pubmed/chemical/MPH1 protein, S cerevisiae, http://linkedlifedata.com/resource/pubmed/chemical/Multiprotein Complexes, http://linkedlifedata.com/resource/pubmed/chemical/RHC18 protein, S cerevisiae, http://linkedlifedata.com/resource/pubmed/chemical/RecQ Helicases, http://linkedlifedata.com/resource/pubmed/chemical/SGS1 protein, S cerevisiae, http://linkedlifedata.com/resource/pubmed/chemical/SMC5 protein, S cerevisiae, http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5119-25
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Homologous recombination-dependent rescue of deficiency in the structural maintenance of chromosomes (Smc) 5/6 complex.
pubmed:affiliation
Department of Pathology and Laboratory Medicine., University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural