Communication between DNA polymerases and Replication Protein A within the archaeal replisome.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39738083.
- Also identified by DOI 10.1038/s41467-024-55365-w and PMC identifier 11686378.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Replication Protein A (RPA) plays a pivotal role in DNA replication by coating and protecting exposed single-stranded DNA, and acting as a molecular hub that recruits additional replication factors. We demonstrate that archaeal RPA hosts a winged-helix domain (WH) that interacts with two key actors of the replisome: the DNA primase (PriSL) and the replicative DNA polymerase (PolD). Using an integrative structural biology approach, combining nuclear magnetic resonance, X-ray crystallography and cryo-electron microscopy, we unveil how RPA interacts with PriSL and PolD through two distinct surfaces of the WH domain: an evolutionarily conserved interface and a novel binding site. Finally, RPA is shown to stimulate the activity of PriSL in a WH-dependent manner. This study provides a molecular understanding of the WH-mediated regulatory activity in central replication factors such as RPA, which regulate genome maintenance in Archaea and Eukaryotes.
Medical subject headings
- Replication Protein A
- DNA Replication
- DNA-Directed DNA Polymerase
- DNA Primase
- Archaeal Proteins
- Cryoelectron Microscopy