Work

Structure of the PCNA unloader Elg1-RFC

Year: 2024

Type: article

Abstract: heteropentamer replication factor C (RFC). PCNA encircling duplex DNA is quite stable and is removed from DNA by the dedicated clamp unloader Elg1-RFC. Here, we show the cryo-EM structure of Elg1-RFC in various states with PCNA. The structures reveal essential features of Elg1-RFC that explain how it is dedicated to PCNA unloading. Specifically, Elg1 contains two external loops that block opening of the Elg1-RFC complex for DNA binding, and an "Elg1 plug" domain that fills the central DNA binding chamber, thereby reinforcing the exclusive PCNA unloading activity of Elg1-RFC. Elg1-RFC was capable of unloading PCNA using non-hydrolyzable AMP-PNP. Both RFC and Elg1-RFC could remove PCNA from covalently closed circular DNA, indicating that PCNA unloading occurs by a mechanism that is distinct from PCNA loading. Implications for the PCNA unloading mechanism are discussed.

Source: Science Advances

DOI: 10.1126/sciadv.adl1739

Authors: Fengwei Zheng, Nina Y. Yao, Roxana E. Georgescu, Huilin Li, Michael E. O’Donnell

Institutions: Van Andel Institute, Howard Hughes Medical Institute, Rockefeller University

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $4,500

Funders: Howard Hughes Medical Institute, National Institutes of Health, National Institute of General Medical Sciences