Role of Homodimerization of Human Cytomegalovirus DNA Polymerase Accessory Protein UL44 in Origin-Dependent DNA Replication in Cells

Role of Homodimerization of Human Cytomegalovirus DNA Polymerase Accessory Protein UL44 in Origin-Dependent DNA Replication in Cells
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DOI:
10.1128/jvi.01193-08
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发表时间:
2008-12-15
影响因子:
5.4
通讯作者:
Loregian, Arianna
Loregian, Arianna
中科院分区:
医学2区
文献类型:
--
作者:
Sinigalia, Elisa;Alvisi, Gualtiero;Loregian, Arianna

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人巨细胞病毒(HCMV)DNA聚合酶的假定持续合成亚基UL 44形成同源二聚体。UL 44的二聚化对于体外结合DNA是重要的;然而,它是否对于细胞环境中的DNA复制也是重要的尚不清楚。在这里,我们表明,二聚化受损但核定位或与聚合酶催化亚基C末端相互作用不受损的UL 44点突变体无法支持细胞中HCMV oriLyt依赖性DNA复制。这些数据表明,UL 44同源二聚体的破坏可能代表一种新的抗HCMV策略。
The presumed processivity subunit of human cytomegalovirus (HCMV) DNA polymerase, UL44, forms homodimers. The dimerization of UL44 is important for binding to DNA in vitro; however, whether it is also important for DNA replication in a cellular context is unknown. Here we show that UL44 point mutants that are impaired for dimerization, but not for nuclear localization or interaction with the C terminus of the polymerase catalytic subunit, are not capable of supporting HCMV oriLyt-dependent DNA replication in cells. These data suggest that the disruption of UL44 homodimers could represent a novel anti-HCMV strategy.