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• W2906265806 abstract "Xeroderma pigmentosum group C (XPC) is a well-known DNA damage recognition protein. Defects in XPC lead to carcinogenesis and progression of many human cancers. In the current study, we defined a novel, important role of XPC in preventing centrosome amplification during cisplatin-mediated DNA damage response. From experiments with human bladder cancer tissue, urothelial tissue from Xpc knockout mice and XPC-silenced cell lines, we found that attenuated XPC expression was associated with increased centrosome amplification in human bladder cancer. A significant increase in centrosome amplification was observed in XPC-silenced cells upon cisplatin treatment. XPC deficiency leads to reduced BRCA1 expression via upregulating its transcriptional repressor, Pit-1. The BRCA1 downregulation results in more DNA double strand breaks accumulation and persistent activation of the ATM-Chk1/Chk2 signaling, resulting in a prolonged G2/M arrest during which centrosome can over-duplicate and lead to centrosome amplification. XPC complementation in silenced cells could reduce Pit-1 expression, increase BRCA1 expression and recover the status of centrosome amplification. Our study reveals a new function for XPC in preventing chromosomal instability, providing new information on cancer chemotherapy and potential clinical significance for cancer management." @default.
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• W2906265806 date "2019-03-01" @default.
• W2906265806 modified "2023-10-18" @default.
• W2906265806 title "XPC deficiency leads to centrosome amplification by inhibiting BRCA1 expression upon cisplatin-mediated DNA damage in human bladder cancer" @default.
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• W2906265806 doi "https://doi.org/10.1016/j.canlet.2018.12.004" @default.
• W2906265806 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30579971" @default.
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