原标题：Review | 抑癌基因p53 及其异构体在DNA双链开裂修正中的效果
p53是一系列被称为肿瘤按捺蛋白（也称为p53蛋白或p53肿瘤蛋白）的同源异构蛋白的总称。该蛋白是最早发现的肿瘤按捺基因所编码的蛋白之一。p53蛋白能调理细胞周期，然后防止细胞癌变发作。p53蛋白能坚持基因组的稳定性，防止或削减骤变的发作，因而被称为基因组守护者。
Cartoon representation of a complex between DNA and the prot
p53蛋白在防止癌症发作机制上扮演重要的人物，例如，细胞凋亡 (apoptosis) 、基因组稳定性 (genetic stability) 、按捺血管重生 (angiogenesis)。 p53蛋白经过下列之组织达到防止癌症发作:
- 当DNA受损时，p53蛋白能活化DNA修正蛋白 (DNA repair proteins)。
- p53蛋白能按捺细胞成长,经过使细胞周期逗留于G1/S的节律点上，以达到DNA损坏辨识。 (若能将细胞于此节律点上逗留够久，DNA修护蛋白将有更富余的时刻修正DNA损坏部位，并持续细胞的成长周期。)
- 若细胞的DNA受损已不能修正，p53蛋白能开始细胞凋亡程序，防止具有不正常遗传资讯的细胞持续割裂成长。
近来，来自浙江大学生命科学学院的研讨团队总述了p53 及其异构体在DNA双链开裂修正中的效果，具体解读了p53在DNA损害修正中的机制。相关论文发表于Journal of Zhejiang University SCIENCE
论文截图
DNA双链开裂是DNA损害最严峻的方式。假如 DNA开裂不能正确修正,将会导致遗传物质的丢掉、基因骤变和染色体重排。这不只会影响正常 的发育和变老进程,并且更严峻的是基因组的不完整会导致人类简单患上免疫缺点、神经系统紊乱和癌症等疾病。抑癌基因p53在DNA损害反响 中扮演着一个中心人物,超越50%以上的人类癌 细胞中p53发作了变异。p53宗族包含p53、p63 和p73三个成员。近年来研讨发现:人的p53基因 最少编码12个异构体,这些异构体在DNA损害反 应中起着不同效果,并协同p53一同保持基因组 DNA的完整性。本总述将讨论p53及其异构体在 DNA双链开裂修正中的效果。
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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