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Binding-Induced Conformational Changes Involved in Sliding Clamp PCNA and DNA Polymerase DPO4.

ABSTRACT: Cooperation between DNA polymerases and DNA sliding clamp proteins is essential for DNA replication and repair. However, it is still challenging to clarify the binding mechanism and the movements of Y-family DNA polymerase IV (DPO4) on the proliferating cell nuclear antigen (PCNA) ring. Here we develop the simulation models of DPO4-PCNA123 and DPO4-PCNA12 complexes and uncover the underlying dynamics of DPO4 during binding and the binding order of the DPO4 domains. Two important intermediate states are found on the free energy surface before reaching the final bound state. Our results suggest that both PCNA3 and DPO4 can influence the PCNA12 planar conformation, whereas the impact of PCNA3 on PCNA12 is more significant than DPO4. These findings provide the crucial information of the conformational dynamics of DPO4 and PCNA, as well as the clue of the underlying mechanism of the cooperation between DPO4 and PCNA during DNA replication.

SUBMITTER: Chu WT

PROVIDER: S-EPMC7229285 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Binding-Induced Conformational Changes Involved in Sliding Clamp PCNA and DNA Polymerase DPO4.

Chu Wen-Ting WT Suo Zucai Z Wang Jin J

iScience 20200501 5

Cooperation between DNA polymerases and DNA sliding clamp proteins is essential for DNA replication and repair. However, it is still challenging to clarify the binding mechanism and the movements of Y-family DNA polymerase IV (DPO4) on the proliferating cell nuclear antigen (PCNA) ring. Here we develop the simulation models of DPO4-PCNA123 and DPO4-PCNA12 complexes and uncover the underlying dynamics of DPO4 during binding and the binding order of the DPO4 domains. Two important intermediate sta ...[more]

PMID: 32422591

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