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dc.contributor.authorPageau, Gayle Jeannette
dc.contributor.authorLawrence, Jeanne B.
dc.date2022-08-11T08:10:05.000
dc.date.accessioned2022-08-23T16:54:45Z
dc.date.available2022-08-23T16:54:45Z
dc.date.issued2006-12-06
dc.date.submitted2008-08-15
dc.identifier.citationJ Cell Biol. 2006 Dec 4;175(5):693-701. <a href="http://dx.doi.org/10.1083/jcb.200602055">Link to article on publisher's site</a>
dc.identifier.issn0021-9525 (Print)
dc.identifier.doi10.1083/jcb.200602055
dc.identifier.pmid17145961
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42575
dc.description.abstractBreast cancer-associated protein 1 (BRCA1) forms foci at sites of induced DNA damage, but any significance of these normal S-phase foci is unknown. BRCA1 distribution does not simply mirror or overlap that of replicating DNA; however, BRCA1 foci frequently abut sites of BrdU incorporation, mostly at mid-to-late S phase. Although BRCA1 does not overlap XIST RNA across the inactive X chromosome, BRCA1 foci position overwhelmingly in heterochromatic regions, particularly the nucleolar periphery where many centromeres reside. In humans and mice, including early embryonic cells, BRCA1 commonly associates with interphase centromere-kinetochore complexes, including pericentric heterochromatin. Proliferating cell nuclear antigen or BrdU labeling demonstrates that BRCA1 localizes adjacent to, or "paints," major satellite blocks as chromocenters replicate, where topoisomerase is also enriched. BRCA1 loss is often associated with proliferative defects, including postmitotic bridges enriched with satellite DNA. These findings implicate BRCA1 in replication-linked maintenance of centric/pericentric heterochromatin and suggest a novel means whereby BRCA1 loss may contribute to genomic instability and cancer.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17145961&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectAnimals
dc.subjectBRCA1 Protein
dc.subjectCell Line
dc.subjectCentromere
dc.subject*DNA Replication
dc.subjectFemale
dc.subjectFibroblasts
dc.subjectHeterochromatin
dc.subjectHumans
dc.subjectInterphase
dc.subjectKinetochores
dc.subjectMice
dc.subject*S Phase
dc.subjectCell Biology
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleBRCA1 foci in normal S-phase nuclei are linked to interphase centromeres and replication of pericentric heterochromatin
dc.typeJournal Article
dc.source.journaltitleThe Journal of cell biology
dc.source.volume175
dc.source.issue5
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1909&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/910
dc.identifier.contextkey579799
refterms.dateFOA2022-08-23T16:54:45Z
html.description.abstract<p>Breast cancer-associated protein 1 (BRCA1) forms foci at sites of induced DNA damage, but any significance of these normal S-phase foci is unknown. BRCA1 distribution does not simply mirror or overlap that of replicating DNA; however, BRCA1 foci frequently abut sites of BrdU incorporation, mostly at mid-to-late S phase. Although BRCA1 does not overlap XIST RNA across the inactive X chromosome, BRCA1 foci position overwhelmingly in heterochromatic regions, particularly the nucleolar periphery where many centromeres reside. In humans and mice, including early embryonic cells, BRCA1 commonly associates with interphase centromere-kinetochore complexes, including pericentric heterochromatin. Proliferating cell nuclear antigen or BrdU labeling demonstrates that BRCA1 localizes adjacent to, or "paints," major satellite blocks as chromocenters replicate, where topoisomerase is also enriched. BRCA1 loss is often associated with proliferative defects, including postmitotic bridges enriched with satellite DNA. These findings implicate BRCA1 in replication-linked maintenance of centric/pericentric heterochromatin and suggest a novel means whereby BRCA1 loss may contribute to genomic instability and cancer.</p>
dc.identifier.submissionpathoapubs/910
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages693-701


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