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Dynamics of open DNA sliding clamps

Journal Article


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Abstract


  • A range of enzymes in DNA replication and repair bind to DNA-clamps: torus-shaped proteins that encircle double-stranded DNA and act as mobile tethers. Clamps from viruses (such as gp45 from the T4 bacteriophage) and eukaryotes (PCNAs) are homotrimers, each protomer containing two repeats of the DNA-clamp motif, while bacterial clamps (pol III β) are homodimers, each protomer containing three DNA-clamp motifs. Clamps need to be flexible enough to allow opening and loading onto primed DNA by clamp loader complexes. Equilibrium and steered molecular dynamics simulations have been used to study DNA-clamp conformation in open and closed forms. The E. coli and PCNA clamps appear to prefer closed, planar conformations. Remarkably, gp45 appears to prefer an open right-handed spiral conformation in solution, in agreement with previously reported biophysical data. The structural preferences of DNA clamps in solution have implications for understanding the duty cycle of clamp-loaders.

Publication Date


  • 2016

Citation


  • Oakley, A. J. (2016). Dynamics of open DNA sliding clamps. PLoS One, 11 (5), e0154899.

Scopus Eid


  • 2-s2.0-84991590449

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=4738&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/3715

Start Page


  • e0154899

Volume


  • 11

Issue


  • 5

Abstract


  • A range of enzymes in DNA replication and repair bind to DNA-clamps: torus-shaped proteins that encircle double-stranded DNA and act as mobile tethers. Clamps from viruses (such as gp45 from the T4 bacteriophage) and eukaryotes (PCNAs) are homotrimers, each protomer containing two repeats of the DNA-clamp motif, while bacterial clamps (pol III β) are homodimers, each protomer containing three DNA-clamp motifs. Clamps need to be flexible enough to allow opening and loading onto primed DNA by clamp loader complexes. Equilibrium and steered molecular dynamics simulations have been used to study DNA-clamp conformation in open and closed forms. The E. coli and PCNA clamps appear to prefer closed, planar conformations. Remarkably, gp45 appears to prefer an open right-handed spiral conformation in solution, in agreement with previously reported biophysical data. The structural preferences of DNA clamps in solution have implications for understanding the duty cycle of clamp-loaders.

Publication Date


  • 2016

Citation


  • Oakley, A. J. (2016). Dynamics of open DNA sliding clamps. PLoS One, 11 (5), e0154899.

Scopus Eid


  • 2-s2.0-84991590449

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=4738&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/3715

Start Page


  • e0154899

Volume


  • 11

Issue


  • 5