Physical Interaction between the Herpes Simplex Virus Type 1 Exonuclease, UL12, and the DNA Double-Strand Break-Sensing MRN Complex

被引:54
作者
Balasubramanian, Nandakumar
Bai, Ping
Buchek, Gregory
Korza, George
Weller, Sandra K. [1 ]
机构
[1] Univ Connecticut, Ctr Hlth, Dept Mol Microbial & Struct Biol, Farmington, CT 06030 USA
关键词
DEPENDENT PROTEIN-KINASE; MISMATCH REPAIR PROTEINS; ALKALINE NUCLEASE; VIRAL-DNA; BINDING-PROTEIN; DAMAGE RESPONSE; REPLICATION COMPARTMENTS; HOMOLOGOUS RECOMBINATION; HETERODUPLEX REJECTION; GEL-ELECTROPHORESIS;
D O I
10.1128/JVI.01506-10
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The herpes simplex virus type 1 (HSV-1) alkaline nuclease, encoded by the UL12 gene, plays an important role in HSV-1 replication, as a UL12 null mutant displays a severe growth defect. The HSV-1 alkaline exonuclease UL12 interacts with the viral single-stranded DNA binding protein ICP8 and promotes strand exchange in vitro in conjunction with ICP8. We proposed that UL12 and ICP8 form a two-subunit recombinase reminiscent of the phage lambda Red alpha/beta recombination system and that the viral and cellular recombinases contribute to viral genome replication through a homologous recombination-dependent DNA replication mechanism. To test this hypothesis, we identified cellular interaction partners of UL12 by using coimmunoprecipitation. We report for the first time a specific interaction between UL12 and components of the cellular MRN complex, an important factor in the ATM-mediated homologous recombination repair (HRR) pathway. This interaction is detected early during infection and does not require viral DNA or other viral or cellular proteins. The region of UL12 responsible for the interaction has been mapped to the first 125 residues, and coimmunoprecipitation can be abolished by deletion of residues 100 to 126. These observations support the hypothesis that cellular and viral recombination factors work together to promote efficient HSV-1 growth.
引用
收藏
页码:12504 / 12514
页数:11
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