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.
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4 December 2006
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December 04 2006
BRCA1 foci in normal S-phase nuclei are linked to interphase centromeres and replication of pericentric heterochromatin
Gayle J. Pageau,
Gayle J. Pageau
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
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Jeanne B. Lawrence
Jeanne B. Lawrence
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
Search for other works by this author on:
Gayle J. Pageau
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
Jeanne B. Lawrence
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
Correspondence to Jeanne B. Lawrence: [email protected]
Abbreviations used in this paper: BRCA, breast cancer–associated protein; CENP, centromere protein; hnRNA, heterogeneous nuclear RNA; MEF, mouse embryo fibroblast; PCH, pericentric heterochromatin; PCNA, proliferating cell nuclear antigen.
Received:
February 10 2006
Accepted:
November 01 2006
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2006
J Cell Biol (2006) 175 (5): 693–701.
Article history
Received:
February 10 2006
Accepted:
November 01 2006
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BRCA1 in replication
Citation
Gayle J. Pageau, Jeanne B. Lawrence; BRCA1 foci in normal S-phase nuclei are linked to interphase centromeres and replication of pericentric heterochromatin . J Cell Biol 4 December 2006; 175 (5): 693–701. doi: https://doi.org/10.1083/jcb.200602055
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