Rad54 Drives ATP Hydrolysis-Dependent DNA Sequence Alignment during Homologous Recombination.

J Brooks Crickard, Corentin J Moevus, Youngho Kwon, Patrick Sung, Eric C Greene

Cell 2020 Jun 11

filter terms:

Homologous recombination (HR) helps maintain genome integrity, and HR defects give rise to disease, especially cancer. During HR, damaged DNA must be aligned with an undamaged template through a process referred to as the homology search. Despite decades of study, key aspects of this search remain undefined. Here, we use single-molecule imaging to demonstrate that Rad54, a conserved Snf2-like protein found in all eukaryotes, switches the search from the diffusion-based pathways characteristic of the basal HR machinery to an active process in which DNA sequences are aligned via an ATP-dependent molecular motor-driven mechanism. We further demonstrate that Rad54 disrupts the donor template strands, enabling the search to take place within a migrating DNA bubble-like structure that is bound by replication protein A (RPA). Our results reveal that Rad54, working together with RPA, fundamentally alters how DNA sequences are aligned during HR. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

J Brooks Crickard, Corentin J Moevus, Youngho Kwon, Patrick Sung, Eric C Greene. Rad54 Drives ATP Hydrolysis-Dependent DNA Sequence Alignment during Homologous Recombination. Cell. 2020 Jun 11;181(6):1380-1394.e18