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dc.contributor.authorKim, Hyun-Minen_US
dc.contributor.authorColaiácovo, Monica P.en_US
dc.date.accessioned2014-11-03T17:40:04Z
dc.date.issued2014en_US
dc.identifier.citationKim, Hyun-Min, and Monica P. Colaiácovo. 2014. “ZTF-8 Interacts with the 9-1-1 Complex and Is Required for DNA Damage Response and Double-Strand Break Repair in the C. elegans Germline.” PLoS Genetics 10 (10): e1004723. doi:10.1371/journal.pgen.1004723. http://dx.doi.org/10.1371/journal.pgen.1004723.en
dc.identifier.issn1553-7390en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13347570
dc.description.abstractGermline mutations in DNA repair genes are linked to tumor progression. Furthermore, failure in either activating a DNA damage checkpoint or repairing programmed meiotic double-strand breaks (DSBs) can impair chromosome segregation. Therefore, understanding the molecular basis for DNA damage response (DDR) and DSB repair (DSBR) within the germline is highly important. Here we define ZTF-8, a previously uncharacterized protein conserved from worms to humans, as a novel factor involved in the repair of both mitotic and meiotic DSBs as well as in meiotic DNA damage checkpoint activation in the C. elegans germline. ztf-8 mutants exhibit specific sensitivity to γ-irradiation and hydroxyurea, mitotic nuclear arrest at S-phase accompanied by activation of the ATL-1 and CHK-1 DNA damage checkpoint kinases, as well as accumulation of both mitotic and meiotic recombination intermediates, indicating that ZTF-8 functions in DSBR. However, impaired meiotic DSBR progression partially fails to trigger the CEP-1/p53-dependent DNA damage checkpoint in late pachytene, also supporting a role for ZTF-8 in meiotic DDR. ZTF-8 partially co-localizes with the 9-1-1 DDR complex and interacts with MRT-2/Rad1, a component of this complex. The human RHINO protein rescues the phenotypes observed in ztf-8 mutants, suggesting functional conservation across species. We propose that ZTF-8 is involved in promoting repair at stalled replication forks and meiotic DSBs by transducing DNA damage checkpoint signaling via the 9-1-1 pathway. Our findings define a conserved function for ZTF-8/RHINO in promoting genomic stability in the germline.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pgen.1004723en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199516/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.titleZTF-8 Interacts with the 9-1-1 Complex and Is Required for DNA Damage Response and Double-Strand Break Repair in the C. elegans Germlineen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Geneticsen
dash.depositing.authorKim, Hyun-Minen_US
dc.date.available2014-11-03T17:40:04Z
dc.identifier.doi10.1371/journal.pgen.1004723*
dash.contributor.affiliatedKim, Hyun-Min
dash.contributor.affiliatedColaiacovo, Monica


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