8thd
Structure of the Saccharomyces cerevisiae clamp unloader Elg1-RFC bound to PCNAStructure of the Saccharomyces cerevisiae clamp unloader Elg1-RFC bound to PCNA
Structural highlights
FunctionRFC4_YEAST Component of ATP-dependent clamp loader (RFC and RFC-like) complexes for DNA clamps, such as the POL30/PCNA homotrimer and the checkpoint clamp DDC1:MEC3:RAD17 complex. During a clamp loading circle, the RFC:clamp complex binds to DNA and the recognition of the double-stranded/single-stranded junction stimulates ATP hydrolysis by RFC. The complex presumably provides bipartite ATP sites in which one subunit supplies a catalytic site for hydrolysis of ATP bound to the neighboring subunit. Dissociation of RFC from the clamp leaves the clamp encircling DNA. Component of the replication factor C (RFC or activator 1) complex which loads POL30/PCNA and acts during elongation of primed DNA templates by DNA polymerase delta and epsilon. RFC has an essential but redundant activity in sister chromatid cohesion establishment. Component of the RFC-like complex CTF18-RFC which is required for efficient establishment of chromosome cohesion during S-phase and may load or unload POL30/PCNA. Component of the RFC-like RAD24-RFC complex which loads the checkpoint clamp DDC1:MEC3:RAD17 complex and is involved in DNA repair pathways. Component of the RFC-like ELG1-RFC complex which appears to have a role in DNA replication, replication fork re-start, recombination and repair.[1] [2] [3] Publication Abstract from PubMedDuring DNA replication, the proliferating cell nuclear antigen (PCNA) clamps are loaded onto primed sites for each Okazaki fragment synthesis by the AAA(+) 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. Structure of the PCNA unloader Elg1-RFC.,Zheng F, Yao NY, Georgescu RE, Li H, O'Donnell ME Sci Adv. 2024 Mar;10(9):eadl1739. doi: 10.1126/sciadv.adl1739. Epub 2024 Mar 1. PMID:38427736[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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