title: Activation of DNA damage repair pathways by murine polyomavirus.
abstract: Nuclear replication of DNA viruses activates DNA damage repair (DDR) pathways, which are thought to detect and inhibit viral replication. However, many DNA viruses also depend on these pathways in order to optimally replicate their genomes. We investigated the relationship between murine polyomavirus (MuPyV) and components of DDR signaling pathways including CHK1, CHK2, H2AX, ATR, and DNAPK. We found that recruitment and retention of DDR proteins at viral replication centers was independent of H2AX, as well as the viral small and middle T-antigens. Additionally, infectious virus production required ATR kinase activity, but was independent of CHK1, CHK2, or DNAPK signaling. ATR inhibition did not reduce the total amount of viral DNA accumulated, but affected the amount of virus produced, indicating a defect in virus assembly. These results suggest that MuPyV may utilize a subset of DDR proteins or non-canonical DDR signaling pathways in order to efficiently replicate and assemble.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology and BioFrontiers Institute, University of Colorado at Boulder, Jennie Smoly Caruthers Biotechnology Building, 3415 Colorado Avenue, Boulder, CO 80303, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Heiser
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology and BioFrontiers Institute, University of Colorado at Boulder, Jennie Smoly Caruthers Biotechnology Building, 3415 Colorado Avenue, Boulder, CO 80303, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Nicholas
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology and BioFrontiers Institute, University of Colorado at Boulder, Jennie Smoly Caruthers Biotechnology Building, 3415 Colorado Avenue, Boulder, CO 80303, USA. Electronic address: Robert.Garcea@Colorado.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Garcea
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D000071877:Checkpoint Kinase 1 / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004279:DNA, Viral; D000070818:Discoidin Domain Receptors / Q000378:metabolism; D051379:Mice; D009154:Mutation; D011120:Polyomavirus / Q000502:physiology*; D027601:Polyomavirus Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D011485:Protein Binding; D015398:Signal Transduction; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D064447:Checkpoint Kinase 2; D000070818:Discoidin Domain Receptors; D064007:Ataxia Telangiectasia Mutated Proteins; D000071877:Checkpoint Kinase 1
keywords: ATR; Checkpoint signaling; DNA damage repair; Polyomavirus; Viral replication