摘要
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.
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。
基金
supported by the National Natural Science Foundation of China(Nos.31571511 and 31871500)
