PRIMPOL competes with RAD51 to resolve G-quadruplexinduced replication stress via its interaction with RPA

查看全文 作　　者：Tingfang [1]Li;Lu [2]Tang;Haomeng [1]Kou;Feng [1,3]Wang 机构地区：[1]Department of Genetics,School of Basic Medical Sciences,The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical,General Hospital,Tianjin Medical University,Tianjin 300070,China;[2]Department of Stomatology,Shengjing Hospital,China Medical University,Shenyang 110004,China;[3]School and Hospital of Stomatology,Tianjin Medical University,Tianjin 300070,China†These authors contributed 出　　处：《Acta Biochimica et Biophysica Sinica》索引2023年第55卷第3期,共10页 基　　金：supported by the grants from the National Natural Science Foundation of China(No.32170762);the Tianjin Health Research Project(No.19YFZCSY00600);the Natural Science Foundation of Tianjin City(No.19JCJQJC63500). 摘　　要：PRIMPOL(primase-polymerase)is a recently discovered DNA primase-polymerase involved in DNA damage tolerance and replication stress response in eukaryotic cells.However,the detailed mechanism of the PRIMPOL response to replication stress remains elusive.Here,we demonstrate that replication-related factors,including replication protein A(RPA),regulate the accumulation of PRIMPOL in subnuclear foci in response to replication stress induced by replication inhibitors.Moreover,PRIMPOL works at G-quadruplexes(G4s)in human cells to resolve the replication stress induced by G4s.The formation of PRIMPOL foci persists throughout the cell cycle.We further demonstrate that PRIMPOL competes with RAD51 to resolve G4-induced replication stress.In conclusion,our results provide novel insight into the mechanism of PRIMPOL in G4s to resolve replication stress and competition between PRIMPOL(repriming)-and RAD51(fork reversal)-mediated pathways,which indicates a new strategy to improve the tumor response to DNA-damaging chemotherapy by targeting the PRIMPOL pathway. 关 键 词：G-QUADRUPLEX PRIMPOL RAD51 replication stress RPA