title: Bypass of a protein barrier by a replicative DNA helicase.
abstract: Replicative DNA helicases generally unwind DNA as a single hexamer that encircles and translocates along one strand of the duplex while excluding the complementary strand (known as steric exclusion). By contrast, large T antigen, 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 large T antigen 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, large T antigen unwinds DNA past a DNA-protein crosslink on the translocation strand, suggesting that the large T antigen ring can open to bypass bulky adducts. Together, our data underscore the profound conservation among replicative helicase mechanisms, and reveal a new level of plasticity in the interactions of replicative helicases with DNA damage.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Hasan
authors.initials: H
authors.lastname: Yardimci
authors.forename: Xindan
authors.initials: X
authors.lastname: Wang
authors.forename: Anna B
authors.initials: AB
authors.lastname: Loveland
authors.forename: Inger
authors.initials: I
authors.lastname: Tappin
authors.forename: David Z
authors.initials: DZ
authors.lastname: Rudner
authors.forename: Jerard
authors.initials: J
authors.lastname: Hurwitz
authors.forename: Antoine M
authors.initials: AM
authors.lastname: van Oijen
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Walter
mesh_terms: D000957:Antigens, Viral, Tumor / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism*; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D018741:Replication Origin / Q000502:physiology; D013539:Simian virus 40 / Q000201:enzymology*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D000957:Antigens, Viral, Tumor; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D014764:Viral Proteins; D004265:DNA Helicases