Unexpected new insights into DNA clamp loaders: Eukaryotic clamp loaders contain a second DNA site for recessed 5′ ends that facilitates repair and signals DNA damage. (18th September 2022)

• Record Type: Journal Article
• Authors: Li, Huilin; O'Donnell, Mike; Kelch, Brian
• Is Part Of: BioEssays. Volume 44:Number 11(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-18
• Subjects: AAA+ oligomers -- 9‐1‐1 clamp -- clamp loader -- DNA repair -- DNA replication -- PCNA clamp -- sliding clamp; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.202200154
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract: Clamp loaders are pentameric AAA+ assemblies that use ATP to open and close circular DNA sliding clamps around DNA. Clamp loaders show homology in all organisms, from bacteria to human. The eukaryotic PCNA clamp is loaded onto 3′ primed DNA by the replication factor C (RFC) hetero‐pentameric clamp loader. Eukaryotes also have three alternative RFC‐like clamp loaders (RLCs) in which the Rfc1 subunit is substituted by another protein. One of these is the yeast Rad24‐RFC (Rad17‐RFC in human) that loads a 9‐1‐1 heterotrimer clamp onto a recessed 5′ end of DNA. Recent structural studies of Rad24‐RFC have discovered an unexpected 5′ DNA binding site on the outside of the clamp loader and reveal how a 5′ end can be utilized for loading the 9‐1‐1 clamp onto DNA. In light of these results, new studies reveal that RFC also contains a 5′ DNA binding site, which functions in gap repair. These studies also reveal many new features of clamp loaders. As reviewed herein, these recent studies together have transformed our view of the clamp loader mechanism. Abstract : Common mechanisms allow clamp loading at different DNA architectures. The clamp loader RFC uses an external DNA binding site to load the sliding clamp PCNA onto a recessed 3′ end of nicked or gapped DNA, while Rad24‐RFC uses the same site to load the 9‐1‐1 clamp onto 5′‐recessed DNA.