A Dimeric Rep Protein Initiates Replication of a Linear Archaeal Virus Genome: Implications for the Rep Mechanism and Viral Replication

Muse Oke, Melina Kerou, Huanting Liu, Xu Peng, Roger A. Garrett, David Prangishvili, James H. Naismith, Malcolm F. White

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

The Rudiviridae are a family of rod-shaped archaeal viruses with covalently closed, linear double-stranded DNA (dsDNA) genomes. Their replication mechanisms remain obscure, although parallels have been drawn to the Poxviridae and other large cytoplasmic eukaryotic viruses. Here we report that a protein encoded in the 34-kbp genome of the rudivirus SIRV1 is a member of the replication initiator (Rep) superfamily of proteins, which initiate rolling-circle replication (RCR) of diverse viruses and plasmids. We show that SIRV Rep nicks the viral hairpin terminus, forming a covalent adduct between an active-site tyrosine and the 5' end of the DNA, releasing a 3' DNA end as a primer for DNA synthesis. The enzyme can also catalyze the joining reaction that is necessary to reseal the DNA hairpin and terminate replication. The dimeric structure points to a simple mechanism through which two closely positioned active sites, each with a single tyrosine residue, work in tandem to catalyze DNA nicking and joining. We propose a novel mechanism for rudivirus DNA replication, incorporating the first known example of a Rep protein that is not linked to RCR. The implications for Rep protein function and viral replication are discussed.

Original languageEnglish
Pages (from-to)925-931
Number of pages7
JournalJournal of Virology
Volume85
Issue number2
DOIs
Publication statusPublished - Jan 2011

Keywords

  • ARCHAEA
  • DNA REPLICATION
  • VIRUS
  • ENDONUCLEASE DOMAIN
  • EUKARYAL VIRUSES
  • ACTIVE-SITE
  • SIRV1
  • CLEAVAGE
  • REP
  • ORIGIN

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  • BBSRC BBS/B/14426: SPORT

    Naismith, J.

    BBSRC

    18/10/0430/04/12

    Project: Standard

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