The Adenovirus E1b55K/E4orf6 Complex Induces Degradation of the

The adenovirus (Ad) E1b55K and E4orf6 gene products assemble an E3 ubiquitin ligase complex that promotes degradation of cellular proteins. Among the known substrates are p53 and the Mre11-Rad50-Nbs1 (MRN) complex. Since members of the RecQ helicase family function together with MRN in genome mainte-nance, we investigated whether adenovirus affects RecQ proteins. We show that Bloom helicase (BLM) is degraded during adenovirus type 5 (Ad5) infection. BLM degradation is mediated by E1b55K/E4orf6 but is independent of MRN. We detected BLM localized at discrete foci around viral replication centers. These studies identify BLM as a new substrate for degradation by the adenovirus E1b55K/E4orf6 complex. Cellular DNA repair proteins are associated with virus in-fection (reviewed in references 37 and 65). While cellular re-pair proteins accumulate at viral replication centers (24, 40, 52, 57, 59, 67, 72) and process viral DNA ends (20, 57), viruses employ multiple strategies to manipulate DNA damage signal-ing and repair pathways (reviewed in references 19 and 65). Infection with adenovirus (Ad) deleted of early region E4 activates the DNA damage response and results in joining o