The molecular coupling between substrate recognition and ATP turnover in a AAA+ hexameric helicase loader

• Published in: eLife Vol. 10
• Main Authors: Puri, Neha, Fernandez, Amy J, O'Shea Murray, Valerie L, McMillan, Sarah, Keck, James L, Berger, James M
• Format: Journal Article
• Language: English
• Published: Cambridge eLife Sciences Publications Ltd 26-05-2021; eLife Sciences Publications, Ltd
• Subjects: AAA+ ATPase; Adenosine triphosphatase; Biochemistry and Chemical Biology; Chromosomes; Deoxyribonucleic acid; DNA; DNA helicase; DNA replication; DnaB helicase; E coli; Efficiency; helicase; Meier-Gorlin syndrome; Proteins; Replication; Sensors; Unwinding
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.64232

In many bacteria and eukaryotes, replication fork establishment requires the controlled loading of hexameric, ring-shaped helicases around DNA by AAA+(ATPases Associated with various cellular Activities) ATPases. How loading factors use ATP to control helicase deposition is poorly understood. Here, we dissect how specific ATPase elements of
Escherichia coli
DnaC, an archetypal loader for the bacterial DnaB helicase, play distinct roles in helicase loading and the activation of DNA unwinding. We have identified a new element, the arginine-coupler, which regulates the switch-like behavior of DnaC to prevent futile ATPase cycling and maintains loader responsiveness to replication restart systems. Our data help explain how the ATPase cycle of a AAA+-family helicase loader is channeled into productive action on its target; comparative studies indicate that elements analogous to the Arg-coupler are present in related, switch-like AAA+ proteins that control replicative helicase loading in eukaryotes, as well as in polymerase clamp loading and certain classes of DNA transposases.