Sunandan Divatia School of Science, SVKM's NMIMS (Deemed to be) University, Mumbai, India.
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A-STAR), Singapore.
Exp Hematol. 2020 Oct;90:12-17. doi: 10.1016/j.exphem.2020.08.009. Epub 2020 Aug 26.
Mammalian Rap1 is a part of the telomere binding complex named shelterin and is one of the most conserved telomeric proteins. With its essential requirement in lower species to its becoming necessary in higher species, it appears to have gained and lost several functions simultaneously evolving with telomeres. Mammalian Rap1 has been reported to play a role in inflammation, metabolism, and oxidative stress. Mammalian Rap1 has also been found to regulate DNA damage response from telomeres in senescent cells. Recently our group uncovered its novel role in stem cell maintenance, and modulation of the chemotherapeutic response. Mechanistically it was found to function as an adaptor via protein-protein interactions and to modulate the response to DNA damage. In the current review we highlight newly identified functions of Rap1 in regulating telomeric and general DNA damage response with its impact at the cellular and organismal levels.
哺乳动物 Rap1 是端粒结合复合物（称为庇护体）的一部分，是最保守的端粒蛋白之一。从低等物种的必需性到高等物种的必要性，它似乎在与端粒一起进化的过程中同时获得和失去了几种功能。已经报道哺乳动物 Rap1 在炎症、代谢和氧化应激中发挥作用。还发现哺乳动物 Rap1 调节衰老细胞中端粒的 DNA 损伤反应。最近，我们小组发现了它在维持干细胞和调节化疗反应中的新作用。从机制上讲，它通过蛋白质-蛋白质相互作用作为衔接蛋白发挥作用，并调节对 DNA 损伤的反应。在当前的综述中，我们强调了 Rap1 调节端粒和一般 DNA 损伤反应的新功能，及其在细胞和机体水平上的影响。
