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Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase

Journal Article


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Abstract


  • The eukaryotic replicative DNA helicase, CMG, unwinds DNA by an unknown mechanism. In some models, CMG encircles and translocates along one strand of DNA while excluding the other strand. In others, CMG encircles and translocates along duplex DNA. To distinguish between these models, replisomes were confronted with strand-specific DNA roadblocks in Xenopus egg extracts. An ssDNA translocase should stall at an obstruction on the translocation strand but not the excluded strand, whereas a dsDNA translocase should stall at obstructions on either strand. We found that replisomes bypass large roadblocks on the lagging strand template much more readily than on the leading strand template. Our results indicate that CMG is a 3′ to 5′ ssDNA translocase, consistent with unwinding via “steric exclusion.” Given that MCM2-7 encircles dsDNA in G1, the data imply that formation of CMG in S phase involves remodeling of MCM2-7 from a dsDNA to a ssDNA binding mode.

Authors


  •   Fu, Yu V. (external author)
  •   Yardimci, Hasan (external author)
  •   Long, David T. (external author)
  •   Ho, The Vinh (external author)
  •   Guainazzi, Angelo (external author)
  •   Bermudez, Vladimir P. (external author)
  •   Hurwitz, Jerard (external author)
  •   van Oijen, Antoine M.
  •   Scharer, Orlando D. (external author)
  •   Walter, Johannes C. (external author)

Publication Date


  • 2011

Published In


Citation


  • Fu, Y. V., Yardimci, H., Long, D. T., Ho, T., Guainazzi, A., Bermudez, V. P., Hurwitz, J., van Oijen, A. M., Scharer, O. D. & Walter, J. C. (2011). Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase. Cell, 146 (6), 931-941.

Scopus Eid


  • 2-s2.0-80052942659

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3192&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2174

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 931

End Page


  • 941

Volume


  • 146

Issue


  • 6

Place Of Publication


  • United States

Abstract


  • The eukaryotic replicative DNA helicase, CMG, unwinds DNA by an unknown mechanism. In some models, CMG encircles and translocates along one strand of DNA while excluding the other strand. In others, CMG encircles and translocates along duplex DNA. To distinguish between these models, replisomes were confronted with strand-specific DNA roadblocks in Xenopus egg extracts. An ssDNA translocase should stall at an obstruction on the translocation strand but not the excluded strand, whereas a dsDNA translocase should stall at obstructions on either strand. We found that replisomes bypass large roadblocks on the lagging strand template much more readily than on the leading strand template. Our results indicate that CMG is a 3′ to 5′ ssDNA translocase, consistent with unwinding via “steric exclusion.” Given that MCM2-7 encircles dsDNA in G1, the data imply that formation of CMG in S phase involves remodeling of MCM2-7 from a dsDNA to a ssDNA binding mode.

Authors


  •   Fu, Yu V. (external author)
  •   Yardimci, Hasan (external author)
  •   Long, David T. (external author)
  •   Ho, The Vinh (external author)
  •   Guainazzi, Angelo (external author)
  •   Bermudez, Vladimir P. (external author)
  •   Hurwitz, Jerard (external author)
  •   van Oijen, Antoine M.
  •   Scharer, Orlando D. (external author)
  •   Walter, Johannes C. (external author)

Publication Date


  • 2011

Published In


Citation


  • Fu, Y. V., Yardimci, H., Long, D. T., Ho, T., Guainazzi, A., Bermudez, V. P., Hurwitz, J., van Oijen, A. M., Scharer, O. D. & Walter, J. C. (2011). Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase. Cell, 146 (6), 931-941.

Scopus Eid


  • 2-s2.0-80052942659

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3192&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2174

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 931

End Page


  • 941

Volume


  • 146

Issue


  • 6

Place Of Publication


  • United States