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A chromatin re-localization screen for the identification of Poly-ADP-ribosylation (PARylation)-dependent DNA repair factors.

ABSTRACT: A chromatin re-localization screen for the identification of Poly-ADP-ribosylation (PARylation)-dependent DNA repair factors.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Chiho Kim

LAB HEAD: Yonghao Yu

PROVIDER: PXD045229 | Pride | 2024-01-26

REPOSITORIES: Pride

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Nimbolide targets RNF114 to induce the trapping of PARP1 and synthetic lethality in <i>BRCA</i>-mutated cancer.

Li Peng P Zhen Yuanli Y Kim Chiho C Liu Zhengshuai Z Hao Jianwei J Deng Heping H Deng Hejun H Zhou Min M Wang Xu-Dong XD Qin Tian T Yu Yonghao Y

Science advances 20231025 43

Recent studies have pointed to PARP1 trapping as a key determinant of the anticancer effects of PARP1 inhibitors (PARPi). We identified RNF114, as a PARylation-dependent, E3 ubiquitin ligase involved in DNA damage response. Upon sensing genotoxicity, RNF114 was recruited, in a PAR-dependent manner, to DNA lesions, where it targeted PARP1 for degradation. The blockade of this pathway interfered with the removal of PARP1 from DNA lesions, leading to profound PARP1 trapping. We showed that a natura ...[more]

PMID: 37878693

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