期刊
VIROLOGY
卷 445, 期 1-2, 页码 35-56出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2013.07.020
关键词
Papillomavirus; El; DNA replication; Helicase; ATPase; Post-translational modifications; Phosphoryaltion; Episome
类别
资金
- US National Institutes of Health [NIH - AI095632]
- Canadian Institutes for Health Research (CIHR)
- Canadian Cancer Society Research Institute (CCSRI)
- Cancer Research Society (CRS)
El, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, El assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of El at the origin and how the enzyme unwinds DNA using a spiral escalator mechanism. El is tightly regulated in vivo, in particular by post-translational modifications that restrict its accumulation in the nucleus. Here we review how different functional domains of El orchestrate viral DNA replication, with an emphasis on their interactions with substrate DNA, host DNA replication factors and modifying enzymes. These studies have made El one of the best characterized helicases and provided unique insights on how PVs usurp different host-cell machineries to replicate and amplify their genome in a tightly controlled manner. (C) 2013 Elsevier Inc. All rights reserved.
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