Human POLD1 modulates cell cycle progression and DNA damage repair.

Human POLD1 modulates cell cycle progression and DNA damage repair.
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DOI:
10.1186/s12858-015-0044-7
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发表时间:
2015-06-19
期刊:
影响因子:
--
通讯作者:
Wang P
Wang P
中科院分区:
生物4区
文献类型:
--
作者:
Song J;Hong P;Liu C;Zhang Y;Wang J;Wang P

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真核生物DNA聚合酶δ(Pol δ)的活性通过影响DNA的复制和修复而在基因组的稳定性中起重要作用。Pol δ的p125催化亚基在人细胞中由POLD 1基因编码。为了阐明POLD1的生物学功能,我们研究了POLD1过表达或下调对细胞增殖、细胞周期进程、DNA合成和H2O2诱导的DNA氧化损伤的影响。分别用POLD1表达质粒和shRNA转染HEK293细胞,观察细胞增殖、细胞周期和DNA合成情况。用POLD 1表达质粒或shRNA转染HEK293细胞。在HEK293细胞中,通过shRNA下调POLD 1抑制细胞增殖、细胞周期进程和DNA合成。然而,POLD1过表达对这些过程没有显着影响。最后,彗星试验表明POLD 1下调导致DNA损伤增加。我们的研究结果表明,人POLD 1在细胞周期进程的调控和DNA损伤修复中起重要作用。
The activity of eukaryotic DNA polymerase delta (Pol δ) plays an essential role in genome stability through its effects on DNA replication and repair. The p125 catalytic subunit of Pol δ is encoded by POLD1 gene in human cells. To clarify biological functions of POLD1, we investigated the effects of POLD1 overexpression or downregulation on cell proliferation, cell cycle progression, DNA synthesis and oxidative DNA damage induced by H2O2. HEK293 cells were transfected with POLD1 expression plasmid or shRNA, cell proliferation, cell cycle progression, and DNA synthesis in HEK293 cells were analyzed. HEK293 cells were transfected with POLD1 expression plasmid or shRNA. POLD1 downregulation by shRNA suppressed cell proliferation, cell cycle progression, and DNA synthesis in HEK293 cells. However, POLD1 overexpression had no significant effects on these processes. Finally, comet assay showed that POLD1 downregulation led to increased DNA damage. Our results suggest that human POLD1 plays important role in the regulation of cell cycle progression and DNA damage repair.
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