title: The interaction of adenovirus E1A with the mammalian protein Ku70/XRCC6.
abstract: Human adenovirus infects terminally differentiated cells and to replicate it must induce S-phase. The chief architects that drive adenovirus-infected cells into S-phase are the E1A proteins, with 5 different isoforms expressed during infection. E1A remodels the infected cell by associating with cellular factors and modulating their activity. The C-terminus of E1A is known to bind to only a handful of proteins. We have identified a novel E1A C-terminus binding protein, Ku70 (XRCC6), which was found to bind directly within the CR4 of E1A from human adenovirus type 5. Depletion of Ku70 reduced virus growth, possibly by activating the DNA damage response pathway. Ku70 was found to localize to viral replication centers and associate with the viral genome. Ku70 was also recruited to cellular cell cycle regulated promoters following viral infection. Our study has identified, for the first time, Ku70 as a novel E1A-binding protein which affects virus life cycle.
authors: Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB, Canada, R3T 2N2.
authors: Jasmine Rae
authors: JR
authors: Frost
authors: Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB, Canada, R3T 2N2.
authors: Oladunni
authors: O
authors: Olanubi
authors: General Byng School, 1250 Beaumont St., Winnipeg, MB, Canada, R3T 0L8.
authors: Stephen Ka-Hon
authors: SK
authors: Cheng
authors: Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB, Canada, R3T 2N2.
authors: Andrea
authors: A
authors: Soriano
authors: Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB, Canada, R3T 2N2.
authors: Leandro
authors: L
authors: Crisostomo
authors: Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB, Canada, R3T 2N2.
authors: Alennie
authors: A
authors: Lopez
authors: Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB, Canada, R3T 2N2. Electronic address: peter.pelka@umanitoba.ca.
authors: Peter
authors: P
authors: Pelka
mesh_terms: D000257:Adenoviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D015967:Gene Expression Regulation, Viral; D006801:Humans; D000072200:Ku Autoantigen / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000072417:Protein Domains; D014779:Virus Replication
chemical_list: D017500:Adenovirus E1A Proteins; D000072200:Ku Autoantigen
keywords: Adenovirus; Cell cycle; DNA damage response; E1A; Ku70; XRCC6