Show simple item record

dc.contributor.authorSubramanian, Len_US
dc.contributor.authorNakamura, TMen_US
dc.date.accessioned2017-03-24T15:12:15Z
dc.date.available2010-01-04en_US
dc.date.issued2010-02-05en_US
dc.date.submitted2017-03-01T08:53:14.693Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/22222
dc.description.abstractATM and ATR are two redundant checkpoint kinases essential for the stable maintenance of telomeres in eukaryotes. Previous studies have established that MRN (Mre11-Rad50-Nbs1) and ATRIP (ATR Interacting Protein) interact with ATM and ATR, respectively, and recruit their partner kinases to sites of DNA damage. Here, we investigated how Tel1(ATM) and Rad3(ATR) recruitment to telomeres is regulated in fission yeast. Quantitative chromatin immunoprecipitation (ChIP) assays unexpectedly revealed that the MRN complex could also contribute to the recruitment of Tel1(ATM) to telomeres independently of the previously established Nbs1 C-terminal Tel1(ATM) interaction domain. Recruitment of Tel1(ATM) to telomeres in nbs1-c60Delta cells, which lack the C-terminal 60 amino acid Tel1(ATM) interaction domain of Nbs1, was dependent on Rad3(ATR)-Rad26(ATRIP), but the kinase domain of Rad3(ATR) was dispensable. Thus, our results establish that the Rad3(ATR)-Rad26(ATRIP) complex contributes to the recruitment of Tel1(ATM) independently of Rad3(ATR) kinase activity, by a mechanism redundant with the Tel1(ATM) interaction domain of Nbs1. Furthermore, we found that the N-terminus of Nbs1 contributes to the recruitment of Rad3(ATR)-Rad26(ATRIP) to telomeres. In response to replication stress, mammalian ATR-ATRIP also contributes to ATM activation by a mechanism that is dependent on the MRN complex but independent of the C-terminal ATM interaction domain of Nbs1. Since telomere protection and DNA damage response mechanisms are very well conserved between fission yeast and mammalian cells, mammalian ATR-ATRIP may also contribute to the recruitment of ATM to telomeres and to sites of DNA damage independently of ATR kinase activity.en_US
dc.description.sponsorshipThis work was supported by UIC start-up fund, Sidney Kimmel Scholar Program, and the NIH grant GM078253 to TMN. LS is supported by a pre-doctoral fellowship from the American Heart Association and the Henrietta Lange Burk Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.format.extente1000839 - ?en_US
dc.languageengen_US
dc.relation.ispartofPLoS Geneten_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.subjectCell Cycle Proteinsen_US
dc.subjectCheckpoint Kinase 2en_US
dc.subjectChromosomal Proteins, Non-Histoneen_US
dc.subjectModels, Biologicalen_US
dc.subjectMutationen_US
dc.subjectProtein Bindingen_US
dc.subjectProtein Kinasesen_US
dc.subjectProtein Structure, Tertiaryen_US
dc.subjectProtein Subunitsen_US
dc.subjectProtein-Serine-Threonine Kinasesen_US
dc.subjectSchizosaccharomycesen_US
dc.subjectSchizosaccharomyces pombe Proteinsen_US
dc.subjectTelomereen_US
dc.titleA kinase-independent role for the Rad3(ATR)-Rad26(ATRIP) complex in recruitment of Tel1(ATM) to telomeres in fission yeast.en_US
dc.typeArticle
dc.rights.holder© 2010 Subramanian, Nakamura
dc.identifier.doi10.1371/journal.pgen.1000839en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/20140190en_US
pubs.issue2en_US
pubs.notesNot knownen_US
pubs.publication-statusPublished onlineen_US
pubs.volume6en_US
dcterms.dateAccepted2010-01-04en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record