生物节律基因Timeless的生物学功能研究进展

Timeless基因广泛分布于生物体中,是主要的生物节律基因之一,它通过与节律基因Per和Cry家族成员的相互作用影响它们的表达水平。Timeless和Tipin能够稳定复制叉,促进姊妹染色单体凝聚,对DNA复制有促进作用;在细胞周期中激活S期检测点,参与ATR-Chk1和ATM-Chk2的DNA损伤修复通路,加强细胞周期的阻滞以修复DNA损伤。Timeless是生物节律和细胞周期的连接者,在多种癌组织(如肝癌、肺癌、乳腺癌、结直肠癌、肾癌和胰腺癌)中的表达水平与癌旁非癌组织相比有差异,提示Timeless表达异常可能与肿瘤的发生和发展相关。

Progress on Biological Function of Circadian Gene Timeless

Timeless is one of the main circadian genes. It interacts with PER and CRY proteins and regulates their expressions level. Timeless also plays an important role in cell cycle, stabilizes replication forks with Tipin and facilitates sister-chromatid cohesion, coordinates intra-S checkpoint. Meanwhile, Timeless is required for ATR- Chkl and ATM-Chk2 pathways of DNA damage response and arrests cell cycle progression to allow the cell to repair its damaged DNA. Timeless directly couples the cell cycle and the circadian cycle and has different functions in different species. Compared to paired non-cancerous tissues, Timeless expresses diversely in different cancerous tissues, such as liver cancer, lung cancer, breast cancer, colorectal cancer, kidney cancer and pancreatic cancer. These evidences suggest that Timeless may be related to tumorigenesis and progression.