Gene interactions and pathways from curated databases and text-mining
EMBO J 2006, PMID: 16628214

A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA damage sites.

Polanowska, Jolanta; Martin, Julie S; Garcia-Muse, Tatiana; Petalcorin, Mark I R; Boulton, Simon J

The BRCA1 tumour suppressor and its heterodimeric partner BARD1 constitute an E3-ubiquitin (Ub) ligase and function in DNA repair by unknown mechanisms. We show here that the Caenorhabditis elegans BRCA1/BARD1 (CeBCD) complex possesses an E3-Ub ligase responsible for ubiquitylation at DNA damage sites following ionizing radiation (IR). The DNA damage checkpoint promotes the association of the CeBCD complex with E2-Ub conjugating enzyme, Ubc5(LET-70), leading to the formation of an active E3-Ub ligase on chromatin following IR. Correspondingly, defects in Ubc5(let-70) or the DNA damage checkpoint genes atl-1 or mre-11 abolish CeBCD-dependent ubiquitylation in vivo. Extending these findings to human cells reveals a requirement for UbcH5c, the MRN complex, gamma-H2AX and a co-dependence for ATM and ATR kinases for BRCA1-dependent ubiquitylation at DNA damage sites. Furthermore, we demonstrate that the DNA damage checkpoint promotes the association between BRCA1 and UbcH5c to form an active E3-Ub ligase on chromatin after IR. These data reveal that BRCA1-dependent ubiquitylation is activated at sites of DNA repair by the checkpoint as part of a conserved DNA damage response.

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Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • IRef Biogrid Interaction: BRCA1 — UBE2D3 (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: UBE2D3 — BRCA1 (in vivo)
  • IRef Hprd Interaction: UBE2D3 — BRCA1 (in vitro)
  • IRef Intact Interaction: HIST1H4A — BRCA1 (physical association, anti bait coimmunoprecipitation)
In total, 2 gene pairs are associated to this article in curated databases