Dataset Information

PC4-mediated Ku PARylation facilitates NHEJ-dependent DNA damage repair

ABSTRACT: Radiotherapy is one of the mainstays for the treatment of hepatocellular carcinoma (HCC); however, a substantial fraction of HCC patients develops radioresistance and eventually suffer from tumour progression or relapse, a major impediment to the use of radiotherapy. One of the main goals in HCC management is to elucidate the mechanisms underlying radioresistance and identify novel therapeutic targets to improve the patients' prognosis. In this study, we report a DNA repair enhancer, human positive cofactor 4 (PC4), that promotes NHEJ-based DNA repair and renders HCC cells resistant to radiation. Mechanistically, PC4 interacts with PARP1 and directs Ku complex PARylation, resulting in successful recruitment of the Ku complex to damaged chromatin and increasing the efficiency of NHEJ repair. Clinically, PC4 is highly expressed in tumour tissues, which is correlated with poor prognosis in HCC patients. Taken together, our data suggest that PC4 is a DNA repair driver that can be targeted to radiosensitize HCC.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Cell Culture

SUBMITTER: Qimei Pan

LAB HEAD: Chummeng Shi

PROVIDER: PXD042218 | Pride | 2023-10-24

REPOSITORIES: Pride

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Source:

			Action	DRS
	Huh7-PC4-IP-MS.msf	Msf
	Huh7-PC4-IP-MS.raw	Raw
	checksum.txt	Txt

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Publications

PC4-mediated Ku complex PARylation facilitates NHEJ-dependent DNA damage repair.

Pan Qimei Q Luo Peng P Shi Chunmeng C

The Journal of biological chemistry 20230710 8

Radiotherapy is one of the mainstay treatments for hepatocellular carcinoma (HCC). However, a substantial number of patients with HCC develop radioresistance and eventually suffer from tumor progression or relapse, which is a major impediment to the use of radiotherapy. Therefore, elucidating the mechanisms underlying radioresistance and identifying novel therapeutic targets to improve patient prognosis are important in HCC management. In this study, using in vitro and in vivo models, laser micr ...[more]

PMID: 37437887

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