Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy is a research paper published in Nature (2005). On theSindex it has a DataRank of 1.3. It has been cited 6,630 times.
Abstract
BRCA1 and BRCA2 are important for DNA double-strand break repair by homologous recombination, and mutations in these genes predispose to breast and other cancers. Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in base excision repair, a key pathway in the repair of DNA single-strand breaks. We show here that BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis. This seems to be because the inhibition of PARP leads to the persistence of DNA lesions normally repaired by homologous recombination. These results illustrate how different pathways cooperate to repair damage, and suggest that the targeted inhibition of particular DNA repair pathways may allow the design of specific and less toxic therapies for cancer.
›Data sources & pipeline
FAIR Checklist
Context only (not used in score)- Has DOI
FAIR checklist signals are shown for context only and do not affect DataRank scoring.
DataRank Breakdown
Base Score Contribution
1.3
From this paper's citation signal
Citation Network Contribution
0
Citation network not refreshed for this result
This paper's DataRank is currently driven only by its base citation score. Citation network data was not refreshed for this result.
Learn more about DataRank methodology →Why this DataRank?
DataRank blends this paper's own citation count with the influence of the papers that cite it. Here, roughly 100% comes from its base citations and 0% from the citation network.
- Base score B(p)
- log1p(citation_count) — grows sub-linearly, so a paper with 1,000 citations is not 10× a paper with 100.
- Network N(p)
- Σ over citers of log1p(Cq) ÷ max(outdegreeq, 1). Being cited by a highly-cited paper with few references counts most.
- Damping factor d = 0.85
- DataRank = (1−d)·B(p) + d·N(p) — the two cards above are each already multiplied by their share.
- Self-citations excluded
- Citers sharing any OpenAlex author ID with this paper are filtered out before the network sum.
Citers are pulled from OpenAlex sorted by cited_by_count:descand capped per paper, so when the cap binds we keep the highest-signal references and the score is reproducible across reruns.