The interaction of adenovirus E1A with the mammalian protein Ku70/XRCC6

- Ku70 was identified as a novel binding partner of adenovirus E1A.
- Ku70 binds directly within CR4 of E1A.
- Ku70 is required for efficient induction of S-phase by E1A and for maximal adenovirus replication.
- Ku70 localizes to viral replication centers and a ssociates with viral DNA.

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.