Show simple item record

dc.contributor.authorAshworth, A
dc.date.accessioned2018-06-11T14:09:02Z
dc.date.issued2004-06
dc.identifier12
dc.identifier.citationHUMAN MOLECULAR GENETICS, 2004, 13 pp. 1241 - 1248
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1830
dc.description.abstractDirect interaction of FANCD2 with BRCA2 in DNA damage response pathways Fanconi anaemia (FA) is a chromosomal instability disorder characterized by cellular sensitivity to DNA interstrand crosslinking agents and a high risk of cancer. Six of the eight proteins encoded by the known FA genes form a nuclear complex which is required for the monoubiquitination of the FANCD2 protein. FANCD2 complexes and colocalizes with BRCA1, but its presumptive role in DNA repair has not yet been clearly defined. We used yeast two-hybrid analysis to test for interaction between FANCD2 and 10 proteins involved in homologous recombination repair. FANCD2 did not interact with RAD51, the five RAD51 paralogs, RAD52, RAD54 or DMC1. However, it bound to a highly conserved C-terminal site in BRCA2 that also binds FANCG/XRCC9. FANCD2 and BRCA2 can be coimmunoprecipitated from cell extracts of both human and Chinese hamster wild-type cells, thus confirming that the interaction occurs in vivo. Formation of nuclear foci of FANCD2 was normal in the BRCA2 mutant CAPAN-1 cells, which indicates that the recruitment of FANCD2 to sites of DNA-repair is independent of wild-type BRCA2 function. FANCD2 colocalized with RAD51 in foci following treatment with mitomycin C or hydroxyurea, and colocalized very tightly with PCNA after treatment with hydroxyurea. These findings suggest that FANCD2 may have a role in the cellular response to stalled replication forks or in the repair of replication-associated double-strand breaks, irrespective of the type of primary DNA lesion.
dc.format.extent1241 - 1248
dc.languageeng
dc.language.isoeng
dc.titleDirect interaction of FANCD2 with BRCA2 in DNA damage response pathways
dc.typeJournal Article
rioxxterms.licenseref.startdate2004-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfHUMAN MOLECULAR GENETICS
pubs.noteskeywords: Fanconi-anemia protein; susceptibility gene brca2; double- strand breaks; nuclear-complex; recombination proteins; positional cloning; replication forks; yeast 2-hybrid; rad51 paralogs; cross-links
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.volume13
pubs.embargo.termsNot known
icr.researchteamGene Functionen_US
dc.contributor.icrauthorAshworth, Alanen


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following collection(s)

Show simple item record