Opening pathways of the DNA clamps proliferating cell nuclear antigen and Rad9-Rad1-Hus1.

ABSTRACT: Proliferating cell nuclear antigen and the checkpoint clamp Rad9-Rad1-Hus1 topologically encircle DNA and act as mobile platforms in the recruitment of proteins involved in DNA damage response and cell cycle regulation. To fulfill these vital cellular functions, both clamps need to be opened and loaded onto DNA by a clamp loader complex-a process, which involves disruption of the DNA clamp's subunit interfaces. Herein, we compare the relative stabilities of the interfaces using the molecular mechanics Poisson-Boltzmann solvent accessible surface method. We identify the Rad9-Rad1 interface as the weakest and, therefore, most likely to open during clamp loading. We also delineate the dominant interface disruption pathways under external forces in multiple-trajectory steered molecular dynamic

SUBMITTER: Xu X 

PROVIDER: S-EPMC3905852 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature