中文摘要：

DNA损伤应激反应是维持基因组稳定性的基石．细胞在长期进化中形成了由损伤监视、周期调控、损伤修复、凋亡诱导等在内的自稳平衡机制．一方面，借助感应、识别并启动精细而复杂的修复机制修复损伤；另一方面，通过DNA损伤应激活化的细胞周期检查点机制，延迟或阻断细胞周期进程，为损伤修复提供时间，使细胞能安全进入新一轮细胞周期；损伤无法修复时则诱导细胞凋亡．DNA双链断裂（double strand breaks，DSBs）是真核基因组后果最严重的损伤类型之一，其修复不利，同肿瘤等人类疾病的发生发展密切相关．新进展揭示：DSBs损伤反应信号分子ATM—Chk2-p53、H2AX等的组成性活化，是肿瘤形成早期所激活的细胞内可诱导的抗癌屏障，其信号网络的精确、精细调控在基因组稳定性维持中发挥重要作用．此外，H1V病毒整合进入宿主细胞基因组的过程也依赖于宿主细胞中ATM介导的DSBs损伤反应信号转导；ATM特异性的小分子抑制剂在抗H1V感染中显示重要的功能意义．文中重点讨论调控DSBs损伤应激反应信号网络的主要研究进展，及其在肿瘤发生、发展及抗H1V感染中的新医学意义．

英文摘要：

The DNA damage response is a cornerstone of genomic stability. The cell utilizes mutiple mechanisms including damage detection, cell cycle regulation, damage repair and apoptosis to keep cell homeostasis. The DNA damage response include several biochemical pathways： first, the recognition and repair of damaged DNA; second, the activation of DNA damage checkpoint, which arrests cell cycle progression so as to provides time for DNA repair and prevention of the transmission of genomic abnormalities to the daughter cells; third, apoptosis, which eliminates serious damaged cells. The double strand break （DSB） is believed to be one of the most severe types of DNA damage, and errors in DSB repair could result in genomic instability that might lead to malignancy. It has been reported recently that constitutive activation of the ATM-Chk2-p53 pathway and phosphorylation of histone H2AX acts as an inducible anti-cancer barrier in the early stages of human tumorigenesis. This ATM-regulated DNA damage response network maintains genomic integrity and delays or prevents cancer by eliciting growth arrest or cell death. In context with a recent report, the ATM-dependent DNA-damage cellular signaling has also been shown to be involved in the integration of human immunodeficiency virus type-1 （HIV-1） into host genomes, and KU55933, a specific ATM inhibitor, attenuated the infection of HIV-1 into host cells. The regulation and mechanisms of the signaling pathways of DSB response, and its role in HIV-1 infection and malignancy genesis were reviewed.