XPC multifaceted roles beyond DNA damage repair: p53-dependent and p53-independent functions of XPC in cell fate decisions

IF 6.4 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research Pub Date : 2022-01-01 DOI:10.1016/j.mrrev.2021.108400

Abir Zebian , Maya El-Dor , Abdullah Shaito , Frédéric Mazurier , Hamid Reza Rezvani , Kazem Zibara

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引用次数: 2

Abstract

Xeroderma pigmentosum group C protein (XPC) acts as a DNA damage recognition factor for bulky adducts and as an initiator of global genome nucleotide excision repair (GG-NER). Novel insights have shown that the role of XPC is not limited to NER, but is also implicated in DNA damage response (DDR), as well as in cell fate decisions upon stress. Moreover, XPC has a proteolytic role through its interaction with p53 and casp-2S. XPC is also able to determine cellular outcomes through its interaction with downstream proteins, such as p21, ARF, and p16. XPC interactions with effector proteins may drive cells to various fates such as apoptosis, senescence, or tumorigenesis. In this review, we explore XPC’s involvement in different molecular pathways in the cell and suggest that XPC can be considered not only as a genomic caretaker and gatekeeper but also as a tumor suppressor and cellular-fate decision maker. These findings envisage that resistance to cell death, induced by DNA-damaging therapeutics, in highly prevalent P53-deficent tumors might be overcome through new therapeutic approaches that aim to activate XPC in these tumors. Moreover, this review encourages care providers to consider XPC status in cancer patients before chemotherapy in order to improve the chances of successful treatment and enhance patients’ survival.

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XPC在DNA损伤修复之外的多面作用:XPC在细胞命运决定中的p53依赖和p53独立功能。

着色性干皮病C组蛋白(XPC)作为大体积加合物的DNA损伤识别因子和全球基因组核苷酸切除修复(GG-NER)的启动器。新的见解表明，XPC的作用不仅限于NER，而且还涉及DNA损伤反应(DDR)，以及细胞在压力下的命运决定。此外，XPC通过与p53和casp-2S的相互作用具有蛋白水解作用。XPC还能够通过与下游蛋白(如p21、ARF和p16)的相互作用来决定细胞结果。XPC与效应蛋白的相互作用可能导致细胞凋亡、衰老或肿瘤发生。在这篇综述中，我们探讨了XPC在细胞中不同分子通路的参与，并提出XPC不仅可以被认为是基因组的看门人和守门人，还可以被认为是肿瘤抑制因子和细胞命运的决策者。这些发现设想，通过旨在激活这些肿瘤中的XPC的新治疗方法，可能克服由dna损伤疗法诱导的高度流行的p53缺陷肿瘤的细胞死亡抗性。此外，本综述鼓励护理人员在化疗前考虑癌症患者的XPC状态，以提高治疗成功的机会，提高患者的生存率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mutation Research-Reviews in Mutation Research 生物-毒理学

CiteScore

12.20

自引率

1.90%

发文量

审稿时长

15.7 weeks

期刊介绍： The subject areas of Reviews in Mutation Research encompass the entire spectrum of the science of mutation research and its applications, with particular emphasis on the relationship between mutation and disease. Thus this section will cover advances in human genome research (including evolving technologies for mutation detection and functional genomics) with applications in clinical genetics, gene therapy and health risk assessment for environmental agents of concern.