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Bypass of a protein barrier by a replicative DNA helicase

Journal Article


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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


  •   Yardimci, Hasan (external author)
  •   Wang, Xindan (external author)
  •   Loveland, Anna B. (external author)
  •   Tappin, Inger (external author)
  •   Rudner, David Z. (external author)
  •   Hurwitz, Jerard (external author)
  •   van Oijen, Antoine M.
  •   Walter, Johannes C. (external author)

Publication Date


  • 2012

Published In


Citation


  • Yardimci, H., Wang, X., Loveland, A. B., Tappin, I., Rudner, D. Z., Hurwitz, J., van Oijen, A. M. & Walter, J. C. (2012). Bypass of a protein barrier by a replicative DNA helicase. Nature, 492 (7428), 205-209.

Scopus Eid


  • 2-s2.0-84871011483

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3180&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2162

Has Global Citation Frequency


Number Of Pages


  • 4

Start Page


  • 205

End Page


  • 209

Volume


  • 492

Issue


  • 7428

Place Of Publication


  • United Kingdom

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


  •   Yardimci, Hasan (external author)
  •   Wang, Xindan (external author)
  •   Loveland, Anna B. (external author)
  •   Tappin, Inger (external author)
  •   Rudner, David Z. (external author)
  •   Hurwitz, Jerard (external author)
  •   van Oijen, Antoine M.
  •   Walter, Johannes C. (external author)

Publication Date


  • 2012

Published In


Citation


  • Yardimci, H., Wang, X., Loveland, A. B., Tappin, I., Rudner, D. Z., Hurwitz, J., van Oijen, A. M. & Walter, J. C. (2012). Bypass of a protein barrier by a replicative DNA helicase. Nature, 492 (7428), 205-209.

Scopus Eid


  • 2-s2.0-84871011483

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3180&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2162

Has Global Citation Frequency


Number Of Pages


  • 4

Start Page


  • 205

End Page


  • 209

Volume


  • 492

Issue


  • 7428

Place Of Publication


  • United Kingdom