Matches in SemOpenAlex for { <https://semopenalex.org/work/W3115433241> ?p ?o ?g. }
- W3115433241 abstract "TP53 deficiency in cancer is associated with poor patient outcomes and resistance to DNA damaging therapies. However, the mechanisms underlying treatment resistance in p53-deficient cells remain poorly characterized. Using live cell imaging of DNA double-strand breaks (DSBs) and cell cycle state transitions, we show that p53-deficient cells exhibit accelerated repair of radiomimetic-induced DSBs arising in S phase. Low-dose DNA-dependent protein kinase (DNA-PK) inhibition increases the S-phase DSB burden in p53-deficient cells, resulting in elevated rates of mitotic catastrophe. However, a subset of p53-deficient cells exhibits intrinsic resistance to radiomimetic-induced DSBs despite DNA-PK inhibition. We show that p53-deficient cells under DNA-PK inhibition utilize DNA polymerase theta (Pol θ)-mediated end joining repair to promote their viability in response to therapy-induced DSBs. Pol θ inhibition selectively increases S-phase DSB burden after radiomimetic therapy and promotes prolonged G2 arrest. Dual inhibition of DNA-PK and Pol θ restores radiation sensitivity in p53-deficient cells as well as in p53-mutant breast cancer cell lines. Thus, combination targeting of DNA-PK- and Pol θ-dependent end joining repair represents a promising strategy for overcoming resistance to DNA damaging therapies in p53-deficient cancers." @default.
- W3115433241 created "2021-01-05" @default.
- W3115433241 creator A5001486790 @default.
- W3115433241 creator A5010214831 @default.
- W3115433241 creator A5025864372 @default.
- W3115433241 creator A5025961147 @default.
- W3115433241 creator A5026014632 @default.
- W3115433241 creator A5030279370 @default.
- W3115433241 creator A5043392476 @default.
- W3115433241 creator A5052738683 @default.
- W3115433241 creator A5058148393 @default.
- W3115433241 creator A5060739449 @default.
- W3115433241 creator A5062067553 @default.
- W3115433241 creator A5068953744 @default.
- W3115433241 creator A5076234244 @default.
- W3115433241 creator A5087134281 @default.
- W3115433241 creator A5088441683 @default.
- W3115433241 date "2020-12-01" @default.
- W3115433241 modified "2023-10-15" @default.
- W3115433241 title "Dual inhibition of DNA-PK and DNA polymerase theta overcomes radiation resistance induced by p53 deficiency" @default.
- W3115433241 cites W1582641126 @default.
- W3115433241 cites W1607267312 @default.
- W3115433241 cites W1976924852 @default.
- W3115433241 cites W1982957001 @default.
- W3115433241 cites W1986018730 @default.
- W3115433241 cites W1986802053 @default.
- W3115433241 cites W1994568630 @default.
- W3115433241 cites W2003581594 @default.
- W3115433241 cites W2005615310 @default.
- W3115433241 cites W2014194664 @default.
- W3115433241 cites W2016492849 @default.
- W3115433241 cites W2024480685 @default.
- W3115433241 cites W2036179093 @default.
- W3115433241 cites W2036270526 @default.
- W3115433241 cites W2054549064 @default.
- W3115433241 cites W2055078984 @default.
- W3115433241 cites W2055187302 @default.
- W3115433241 cites W2064795157 @default.
- W3115433241 cites W2068371312 @default.
- W3115433241 cites W2079852484 @default.
- W3115433241 cites W2081894694 @default.
- W3115433241 cites W2094192074 @default.
- W3115433241 cites W2106070783 @default.
- W3115433241 cites W2108068107 @default.
- W3115433241 cites W2114843025 @default.
- W3115433241 cites W2117240918 @default.
- W3115433241 cites W2122254308 @default.
- W3115433241 cites W2125486087 @default.
- W3115433241 cites W2130266193 @default.
- W3115433241 cites W2149441684 @default.
- W3115433241 cites W2150183586 @default.
- W3115433241 cites W2154745425 @default.
- W3115433241 cites W2157936422 @default.
- W3115433241 cites W2167097026 @default.
- W3115433241 cites W2167908994 @default.
- W3115433241 cites W2319056895 @default.
- W3115433241 cites W2391227084 @default.
- W3115433241 cites W2476261929 @default.
- W3115433241 cites W2522427913 @default.
- W3115433241 cites W2613362156 @default.
- W3115433241 cites W2625452721 @default.
- W3115433241 cites W2737595608 @default.
- W3115433241 cites W2752942423 @default.
- W3115433241 cites W2765400887 @default.
- W3115433241 cites W2767182262 @default.
- W3115433241 cites W2792097635 @default.
- W3115433241 cites W2796153844 @default.
- W3115433241 cites W2804348137 @default.
- W3115433241 cites W2883592521 @default.
- W3115433241 cites W2888656264 @default.
- W3115433241 cites W2908842729 @default.
- W3115433241 cites W2917824877 @default.
- W3115433241 cites W2920207301 @default.
- W3115433241 cites W2952232866 @default.
- W3115433241 cites W2964649258 @default.
- W3115433241 cites W2968120913 @default.
- W3115433241 cites W2971678986 @default.
- W3115433241 cites W2974447633 @default.
- W3115433241 cites W2976720471 @default.
- W3115433241 cites W3014334593 @default.
- W3115433241 cites W3092794318 @default.
- W3115433241 cites W3093006386 @default.
- W3115433241 doi "https://doi.org/10.1093/narcan/zcaa038" @default.
- W3115433241 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7751686" @default.
- W3115433241 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33385162" @default.
- W3115433241 hasPublicationYear "2020" @default.
- W3115433241 type Work @default.
- W3115433241 sameAs 3115433241 @default.
- W3115433241 citedByCount "14" @default.
- W3115433241 countsByYear W31154332412021 @default.
- W3115433241 countsByYear W31154332412022 @default.
- W3115433241 countsByYear W31154332412023 @default.
- W3115433241 crossrefType "journal-article" @default.
- W3115433241 hasAuthorship W3115433241A5001486790 @default.
- W3115433241 hasAuthorship W3115433241A5010214831 @default.
- W3115433241 hasAuthorship W3115433241A5025864372 @default.
- W3115433241 hasAuthorship W3115433241A5025961147 @default.
- W3115433241 hasAuthorship W3115433241A5026014632 @default.
- W3115433241 hasAuthorship W3115433241A5030279370 @default.
- W3115433241 hasAuthorship W3115433241A5043392476 @default.