Role of p21WAF1 in the Cellular Response to UV
Role of p21WAF1 in the Cellular Response to UV
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DOI：
10.4161/cc.3.2.658
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发表时间：
2004-02
期刊：
影响因子：
4.3
通讯作者：
R. Fotedar;M. Bendjennat;A. Fotedar
中科院分区：
文献类型：
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作者：
R. Fotedar;M. Bendjennat;A. Fotedar
紫外线或伽马辐射介导的DNA损伤激活p53并诱导细胞周期阻滞。DNA损伤后p53诱导细胞周期蛋白依赖性激酶抑制剂p21WAF1在伽马辐射后细胞周期阻滞中起重要作用。p53介导的细胞周期阻滞已被假定为允许细胞修复DNA损伤。紫外线损伤DNA的修复主要通过核苷酸切除途径（NER）进行。已知p21WAF1结合PCNA并抑制PCNA在DNA复制中的功能。PCNA也是NER修复所必需的，但关于p21是否能抑制PCNA在NER中的功能，一直有相互矛盾的报道。因此，很难将p21诱导的细胞周期阻滞与紫外线损伤DNA的修复结合起来。最近的一项研究报道，p21WAF1蛋白在低剂量而不是高剂量的紫外线照射下降解，紫外线后的细胞周期阻滞与p21无关，在低剂量紫外线照射下，p21的降解对最佳DNA修复至关重要。这些发现揭示了p21在细胞对紫外线反应中的作用，并澄清了有关p21功能的一些悬而未决的问题。
UV or gamma irradiation mediated DNA damage activates p53 and induces cell cycle arrest. Induction of cyclin-dependent kinase inhibitor p21WAF1 by p53 after DNA damage plays an important role in cell cycle arrest after gamma irradiation. The p53 mediated cell cycle arrest has been postulated to allow cells to repair the DNA damage. Repair of UV damaged DNA occurs primarily by the nucleotide excision pathway (NER). It is known that p21WAF1 binds PCNA and inhibits PCNA function in DNA replication. PCNA is also required for repair by NER but there have been conflicting reports on whether p21 can inhibit PCNA function in NER. It has therefore been difficult to integrate the UV induced cell cycle arrest by p21 in the context of repair of UV damaged DNA. A recent study reported that p21WAF1 protein is degraded after low but not high doses of UV irradiation, that cell cycle arrest after UV is p21 independent, and that at low dose UV irradiation p21 degradation is essential for optimal DNA repair. These findings shed new light on the role of p21 in the cellular response to UV and clarify some outstanding issues concerning p21 function.