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Differential activation of intra-S-phase checkpoint in response to tripchlorolide and its effects on DNA replication

查看全文 作　　者：YanREN [1]JiaRuiWU 高影响力作者 机构地区：[1]LaboratoryofMolecularCellBiology,InstituteofBiochemistryandCellBiology,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyofSciences,320YueyangRoad,Shanghai200031,China.高影响力机构 出　　处：《Cell Research》索引2004年第14卷第3期,共7页高影响力期刊 基　　金：This work was supported by a grant from the National Natural Science Foundation of China(No.30230110);a special grant from the Major State Basic Research Pro-gram of China(No.G1999053901);a grant from the Chinese Academy of Sciences(No.KSCX2-SW-203)to Jia Rui WU. 摘　　要：DNA replication is tightly regulated during the S phase of the cell cycle, and the activation of the intra-S-phase checkpoint due to DNA damage usually results in arrest of DNA synthesis. However, the molecular details about the correlation between the checkpoint and regulation of DNA replication are still unclear. To investigate the connections between DNA replication and DNA damage checkpoint, a DNA-damage reagent, tripchlorolide, was applied to CHO (Chinese ovary hamster) cells at early- or middle-stages of the S phase. The early-S-phase treatment with TC significantly delayed the progression of the S phase and caused the phosphorylation of the Chk1 checkpoint protein, whereas the middle-S-phase treatment only slightly slowed down the progression of the S phase. Furthermore, the analysis of DNA replication patterns revealed that replication pattern Ⅱ was greatly prolonged in the cells treated with the drug during the early-S phase, whereas the late-replication patterns of these cells were hardly detected, suggesting that the activation of the intra-S-phase checkpoint inhibits the late-origin firing of DNA replication. We conclude that cells at different stages of the S phase are differentially sensitive to the DNA-damage reagent, and the activation of the intra-Sphase checkpoint blocks the DNA replication progression in the late stage of S phase. 关 键 词：DNA 复制 脱氧核糖核酸 损伤 细胞周期
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