A dimeric Rep protein initiates replication of a linear archaeal virus genome: implications for the Rep mechanism and viral replication
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A dimeric Rep protein initiates replication of a linear archaeal virus genome: implications for the Rep mechanism and viral replication. / Oke, Muse; Kerou, Melina; Liu, Huanting; Peng, Xu; Garrett, Roger Antony; Prangishvili, David; Naismith, James H; White, Malcolm F.
In: Journal of Virology, Vol. 85, No. 2, 2011, p. 925-31.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A dimeric Rep protein initiates replication of a linear archaeal virus genome: implications for the Rep mechanism and viral replication
AU - Oke, Muse
AU - Kerou, Melina
AU - Liu, Huanting
AU - Peng, Xu
AU - Garrett, Roger Antony
AU - Prangishvili, David
AU - Naismith, James H
AU - White, Malcolm F
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - DNA Helicases
KW - DNA, Viral
KW - Models, Biological
KW - Protein Multimerization
KW - Rudiviridae
KW - Trans-Activators
KW - Viral Proteins
KW - Virus Replication
U2 - 10.1128/JVI.01467-10
DO - 10.1128/JVI.01467-10
M3 - Journal article
C2 - 21068244
VL - 85
SP - 925
EP - 931
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 2
ER -
ID: 33493706