the hsv-1 exonuclease, ul12, stimulates recombination by a single strand annealing mechanism1型单纯疱疹病毒核酸外切酶、ul12刺激由单一链重组退火机制.pdfVIP

The HSV-1 Exonuclease, UL12, Stimulates Recombination by a Single Strand Annealing Mechanism 1 1 2 2 3 April J. Schumacher , Kareem N. Mohni , Yinan Kan , Eric A. Hendrickson , Jeremy M. Stark , Sandra K. Weller1* 1 Molecular, Microbial and Structural Biology Department, University of Connecticut Health Center, Farmington, Connecticut, United States of America, 2 Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America, 3 Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California, United States of America Abstract Production of concatemeric DNA is an essential step during HSV infection, as the packaging machinery must recognize longer-than-unit-length concatemers; however, the mechanism by which they are formed is poorly understood. Although it has been proposed that the viral genome circularizes and rolling circle replication leads to the formation of concatemers, several lines of evidence suggest that HSV DNA replication involves recombination-dependent replication reminiscent of bacteriophages l and T4. Similar to l, HSV-1 encodes a 59-to-39 exonuclease (UL12) and a single strand annealing protein [SSAP (ICP8)] that interact with each other and can perform strand exchange in vitro. By analogy with l phage, HSV may utilize viral and/or cellular recombination proteins during DNA replication. At least four double strand break repair pathways are present in eukaryotic cells, and HSV-1 is known to manipulate several components of these pathways. Chromosomally integrated reporter assays were used to measure the repair of double strand breaks in HSV-infected cells. Single strand