p53是一系列被称为肿瘤抑制蛋白（也称为p53蛋白或p53肿瘤蛋白）的同源异构蛋白的统称。该蛋白是最早发现的肿瘤抑制基因所编码的蛋白之一。p53蛋白能调节细胞周期，从而避免细胞癌变发生。p53蛋白能保持基因组的稳定性，避免或减少突变的发生，因此被称为基因组守护者。

Cartoon representation of a complex between DNA and the prot

p53蛋白在避免癌症发生机制上扮演重要的角色，例如，细胞凋亡 (apoptosis) 、基因组稳定性 (genetic stability) 、抑制血管新生 (angiogenesis)。 p53蛋白通过下列之机构达成避免癌症发生:

近来，来自浙江大学生命科学学院的研究团队综述了p53 及其异构体在DNA双链断裂修复中的作用，详细解读了p53在DNA损伤修复中的机制。相关论文发表于Journal of Zhejiang University SCIENCE

论文截图

DNA双链断裂是DNA损伤最严重的形式。如果 DNA断裂不能正确修复,将会导致遗传物质的丢失、基因突变和染色体重排。这不仅会影响正常 的发育和衰老过程,而且更严重的是基因组的不完整会导致人类容易患上免疫缺陷、神经系统紊乱和癌症等疾病。抑癌基因p53在DNA损伤反应 中扮演着一个中心角色,超过50%以上的人类癌 细胞中p53发生了变异。p53家族包括p53、p63 和p73三个成员。近年来研究发现:人的p53基因 最少编码12个异构体,这些异构体在DNA损伤反 应中起着不同作用,并协同p53一起维持基因组 DNA的完整性。本综述将探讨p53及其异构体在 DNA双链断裂修复中的作用。

Human p53 and its isoforms

(a) Diagram of human p53 gene structure. Alternative promoters (P1, P1', and P2) and alternative splicing sites (β, γ) areindicated. (b) p53 protein isoforms. TAD: transactivation domain; PXXP: proline-rich domain; DBD: DNA-binding domain;NLS: nuclear localization signal; OD: oligomerization domain; CTD: C-terminal regulatory domain

A model for the p53 signal to protect genomic integrity upon

Abstract

DNA double-stranded break (DSB) is one of the most catastrophic damages of genotoxic insult. Inappropriate repair of DNA DSBs results in the loss of genetic information, mutation, and the generation of harmful genomic rearrangements, which predisposes an organism to immunodeficiency, neurological damage, and cancer. The tumor repressor p53 plays a key role in DNA damage response, and has been found to be mutated in 50% of human cancer. p53, p63, and p73 are three members of the p53 gene family. Recent discoveries have shown that human p53 gene encodes at least 12 isoforms. Different p53 members and isoforms play various roles in orchestrating DNA damage response to maintain genomic integrity. This review briefly explores the functions of p53 and its isoforms in DNA DSB repair.

参考文献:

Y. Cho, S. Gorina, P. D. Jeffrey, N. P. Pavletich. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science (New York, N.Y.). 1994-07-15, 265 (5170): 346–355 [2019-05-26]. ISSN 0036-8075. PMID 8023157.

Yu-Xi Zhang, Wen-Ya Pan, Jun Chen. p53 and its isoforms in DNA double-stranded break repair[J]. Journal of Zhejiang University Science B, 2019, 20(6): 457-466.

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