Human Stnl protects telomere integrity by promoting efficient lagging-strand synthesis at telomeres and mediating C-strand fill-in  

作　　者：Chenhui Huang Xueyu Dai Weihang Chai 

机构地区：[1]School of Molecular Blosclences, WWAMI Medical Education Program, Washington State University, PO Box 1495, Spokane, WA99210, USA

出　　处：《Cell Research》2012年第12期1681-1695,共15页细胞研究（英文版）

摘　　要：Telomere maintenance is critical for genome stability. The newly-identified Ctcl/Stnl/Tenl complex is important for telomere maintenance, though its precise role is unclear. We report here that depletion of hStnl induces cata- strophic telomere shortening, DNA damage response, and early senescence in human somatic cells. These pheno- types are likely due to the essential role of hStnl in promoting efficient replication of lagging-strand telomeric DNA. Downregulation of hStnl accumulates single-stranded G-rich DNA specifically at lagging-strand telomeres, increases telomere fragility, hinders telomere DNA synthesis, as well as delays and compromises telomeric C-strand synthesis. We further show that hStnl deficiency leads to persistent and elevated association of DNA polymerase a （pole） to telomeres, suggesting that hStnl may modulate the DNA synthesis activity of pola rather than controlling the load- ing of pola to telomeres. Additionally, our data suggest that hStnl is unlikely to he part of the telomere capping com- plex. We propose that the hStnl assists DNA polymerases to efficiently duplicate lagging-strand telomeres in order to achieve complete synthesis of telomeric DNA, therefore preventing rapid telomere loss.

关 键 词：Stnl telomere replication G-overhang polct 

分 类 号：Q78[生物学—分子生物学] S831.2[农业科学—畜牧学]