ArticleMolecular cancer research : MCR2014
Base excision repair defects invoke hypersensitivity to PARP inhibition.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 86 citations in OpenAlex.
- The chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage.Nucleic acids research · 2025Article
- Short-term consumption of the modified standard American diet perturbed the metabolic balance and altered DNA damage in MMTV-PyMT transgenic mice.Breast cancer research : BCR · 2025Article
- PARP inhibitor response is enhanced in prostate cancer when XRCC1 expression is reduced.NAR cancer · 2025Article
- Review
- Article
- Article
- Harnessing the effects of hypoxia-like inhibition on homology-directed DNA repair.Seminars in cancer biology · 2024Review
- Temporal recruitment of base excision DNA repair factors in living cells in response to different micro-irradiation DNA damage protocols.DNA repair · 2023Article
- Roles of DNA damage repair and precise targeted therapy in renal cancer (Review).Oncology reports · 2022Article
- BMN673 Is a PARP Inhibitor with Unique Radiosensitizing Properties: Mechanisms and Potential in Radiation Therapy.Cancers · 2022Review
- Targeting the DNA Damage Response Pathways and Replication Stress in Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- XRCC1 counteracts poly(ADP ribose)polymerase (PARP) poisons, olaparib and talazoparib, and a clinical alkylating agent, temozolomide, by promoting the removal of trapped PARP1 from broken DNA.Genes to cells : devoted to molecular & cellular mechanisms · 2022Article
- Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification.Cancer research · 2022Article
- Inhibition of EZH2 transactivation function sensitizes solid tumors to genotoxic stress.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The potential of PARP inhibitors in targeted cancer therapy and immunotherapy.Frontiers in molecular biosciences · 2022Review
- Immediate-Early, Early, and Late Responses to DNA Double Stranded Breaks.Frontiers in genetics · 2022Review
- Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NADCell reports · 2021Article
- Replication gaps are a key determinant of PARP inhibitor synthetic lethality with BRCA deficiency.Molecular cell · 2021Article
- XRCC1 prevents toxic PARP1 trapping during DNA base excision repair.Molecular cell · 2021Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledPARP-1 is important for the recognition of both endogenous and exogenous DNA damage, and binds to DNA strand breaks including intermediates of base excision repair (BER). Once DNA-bound, PARP-1 becomes catalytically activated synthesizing PAR polymers onto itself and other repair factors (PARylation). As a result, BER repair proteins such as XRCC1 and DNA polymerase β (pol β) are more efficiently and rapidly recruited to sites of DNA damage. In the presence of an inhibitor of PARP activity (PARPi), PARP-1 binds to sites of DNA damage, but PARylation is prevented. BER enzyme recruitment is hindered, but binding of PARP-1 to DNA is stabilized, impeding DNA repair and leading to double-strand DNA breaks (DSB). Deficiencies in pol β(-/-) and Xrcc1(-/-) cells resulted in hypersensitivity to the PARP inhibitor 4-AN and reexpression of pol β or XRCC1, in these contexts, reversed the 4-AN hypersensitivity phenotype. BER deficiencies also showed evidence of replication defects that lead to DSB-induced apoptosis upon PARPi treatment. Finally, the clinically relevant PARP inhibitors olaparib and veliparib also exhibited hypersensitivity in both pol β(-/-) and Xrcc1(-/-) BER-deficient cells. These results reveal heightened sensitivity to PARPi as a function of BER deficiency. IMPLICATIONS: BER deficiency represents a new therapeutic opportunity to enhance PARPi efficacy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.