Rad54 Drives ATP Hydrolysis-Dependent DNA Sequence Alignment during Homologous Recombination.
Cell
; 181(6): 1380-1394.e18, 2020 06 11.
Article
em En
| MEDLINE
| ID: mdl-32502392
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.
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MEDLINE
Assunto principal:
DNA
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Trifosfato de Adenosina
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DNA Helicases
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Proteínas de Saccharomyces cerevisiae
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Enzimas Reparadoras do DNA
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Recombinação Homóloga
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article