Yardimci, HasanWang, XindanLoveland, Anna BarbaraTappin, IngerRudner, DavidHurwitz, Jerardvan Oijen, Antoine M.Walter, Johannes C.2014-02-132012Yardimci, Hasan, Xindan Wang, Anna B. Loveland, Inger Tappin, David Z. Rudner, Jerard Hurwitz, Antoine M. van Oijen, and Johannes C. Walter. 2012. “Bypass of a protein roadblock by a replicative DNA helicase.” Nature 492 (7428): 205-209. doi:10.1038/nature11730. http://dx.doi.org/10.1038/nature11730.0028-0836http://nrs.harvard.edu/urn-3:HUL.InstRepos:11708610Replicative DNA helicases generally unwind DNA as a single hexamer that encircles and translocates along one strand of the duplex while excluding the complementary strand (“steric exclusion”). In contrast, large T antigen (T-ag), the replicative DNA helicase of the Simian Virus 40 (SV40), is reported to function as a pair of stacked hexamers that pumps double-stranded DNA through its central channel while laterally extruding single-stranded DNA. Here, we use single-molecule and ensemble assays to show that T-ag assembled on the SV40 origin unwinds DNA efficiently as a single hexamer that translocates on single-stranded DNA in the 3′ to 5′ direction. Unexpectedly, T-ag unwinds DNA past a DNA-protein crosslink on the translocation strand, suggesting that the T-ag ring can open to bypass bulky adducts. Together, our data underscore the profound conservation among replicative helicase mechanisms while revealing a new level of plasticity in their interactions with DNA damage.en-USJournal Article2014-02-1310.1038/nature11730