Matches in SemOpenAlex for { <https://semopenalex.org/work/W3159852022> ?p ?o ?g. }
- W3159852022 abstract "CX-5461 is a G-quadruplex (G4) ligand currently in trials with initial indications of clinical activity in cancers with defects in homologous recombination repair. To identify more genetic defects that could sensitize tumors to CX-5461, we tested synthetic lethality for 480 DNA repair and genome maintenance genes to CX-5461, pyridostatin (PDS), a structurally unrelated G4-specific stabilizer, and BMH-21, which binds GC-rich DNA but not G4 structures. We identified multiple members of HRD, Fanconi Anemia pathways, and POLQ, a polymerase with a helicase domain important for G4 structure resolution. Significant synthetic lethality was observed with UBE2N and RNF168, key members of the DNA damage response associated ubiquitin signaling pathway. Loss-of-function of RNF168 and UBE2N resulted in significantly lower cell survival in the presence of CX-5461 and PDS but not BMH-21. RNF168 recruitment and histone ubiquitination increased with CX-5461 treatment, and nuclear ubiquitination response frequently co-localized with G4 structures. Pharmacological inhibition of UBE2N acted synergistically with CX-5461. In conclusion, we have uncovered novel genetic vulnerabilities to CX-5461 with potential significance for patient selection in future clinical trials." @default.
- W3159852022 created "2021-05-10" @default.
- W3159852022 creator A5001336010 @default.
- W3159852022 creator A5010980483 @default.
- W3159852022 creator A5018093835 @default.
- W3159852022 creator A5031406643 @default.
- W3159852022 creator A5052663562 @default.
- W3159852022 creator A5074271128 @default.
- W3159852022 creator A5080949602 @default.
- W3159852022 date "2021-05-07" @default.
- W3159852022 modified "2023-09-28" @default.
- W3159852022 title "Ubiquitin-mediated DNA damage response is synthetic lethal with G-quadruplex stabilizer CX-5461" @default.
- W3159852022 cites W1450574606 @default.
- W3159852022 cites W1813751289 @default.
- W3159852022 cites W1826222652 @default.
- W3159852022 cites W1840855988 @default.
- W3159852022 cites W1859576021 @default.
- W3159852022 cites W1915704240 @default.
- W3159852022 cites W1963434741 @default.
- W3159852022 cites W1968342623 @default.
- W3159852022 cites W1969513645 @default.
- W3159852022 cites W1973030224 @default.
- W3159852022 cites W1973260880 @default.
- W3159852022 cites W1974755980 @default.
- W3159852022 cites W1982846895 @default.
- W3159852022 cites W1988259427 @default.
- W3159852022 cites W1988617344 @default.
- W3159852022 cites W1989277387 @default.
- W3159852022 cites W1990635146 @default.
- W3159852022 cites W1991580205 @default.
- W3159852022 cites W1991616035 @default.
- W3159852022 cites W1991754576 @default.
- W3159852022 cites W1993259584 @default.
- W3159852022 cites W1999100743 @default.
- W3159852022 cites W2011428226 @default.
- W3159852022 cites W2012214305 @default.
- W3159852022 cites W2020426424 @default.
- W3159852022 cites W2027696068 @default.
- W3159852022 cites W2031991695 @default.
- W3159852022 cites W2040614735 @default.
- W3159852022 cites W2043398720 @default.
- W3159852022 cites W2043652375 @default.
- W3159852022 cites W2054547085 @default.
- W3159852022 cites W2054918042 @default.
- W3159852022 cites W2073722866 @default.
- W3159852022 cites W2078709018 @default.
- W3159852022 cites W2083229398 @default.
- W3159852022 cites W2084377803 @default.
- W3159852022 cites W2087786864 @default.
- W3159852022 cites W2092424765 @default.
- W3159852022 cites W2093320042 @default.
- W3159852022 cites W2096657666 @default.
- W3159852022 cites W2100122648 @default.
- W3159852022 cites W2102212065 @default.
- W3159852022 cites W2103562758 @default.
- W3159852022 cites W2114843025 @default.
- W3159852022 cites W2128800470 @default.
- W3159852022 cites W2131827278 @default.
- W3159852022 cites W2139094585 @default.
- W3159852022 cites W2146589536 @default.
- W3159852022 cites W2146805637 @default.
- W3159852022 cites W2148660588 @default.
- W3159852022 cites W2148879566 @default.
- W3159852022 cites W2149441684 @default.
- W3159852022 cites W2151510603 @default.
- W3159852022 cites W2155773930 @default.
- W3159852022 cites W2156174123 @default.
- W3159852022 cites W2157339938 @default.
- W3159852022 cites W2157570211 @default.
- W3159852022 cites W2157624583 @default.
- W3159852022 cites W2164144387 @default.
- W3159852022 cites W2165260654 @default.
- W3159852022 cites W2168335693 @default.
- W3159852022 cites W2169385687 @default.
- W3159852022 cites W2170551349 @default.
- W3159852022 cites W2171955018 @default.
- W3159852022 cites W2180291937 @default.
- W3159852022 cites W2207187217 @default.
- W3159852022 cites W2208555666 @default.
- W3159852022 cites W2275411324 @default.
- W3159852022 cites W2315475605 @default.
- W3159852022 cites W2470218763 @default.
- W3159852022 cites W2476261929 @default.
- W3159852022 cites W2477532021 @default.
- W3159852022 cites W2478314490 @default.
- W3159852022 cites W2520749639 @default.
- W3159852022 cites W2542071790 @default.
- W3159852022 cites W2588267243 @default.
- W3159852022 cites W2593857065 @default.
- W3159852022 cites W2593966541 @default.
- W3159852022 cites W2602200537 @default.
- W3159852022 cites W2727479110 @default.
- W3159852022 cites W2736256689 @default.
- W3159852022 cites W2743024582 @default.
- W3159852022 cites W2760582164 @default.
- W3159852022 cites W2772524563 @default.
- W3159852022 cites W2805379633 @default.
- W3159852022 cites W2889194247 @default.
- W3159852022 cites W2890810370 @default.
- W3159852022 cites W2891084898 @default.