A Polar and Nucleotide-Dependent Mechanism of Action for RAD51 Paralogs in RAD51 Filament Remodeling
| Autoři | |
|---|---|
| Rok publikování | 2016 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Molecular Cell |
| Fakulta / Pracoviště MU | |
| Citace | |
| Doi | http://dx.doi.org/10.1016/j.molcel.2016.10.020 |
| Obor | Genetika a molekulární biologie |
| Klíčová slova | SINGLE-STRANDED-DNA; INDUCED FLUORESCENCE ENHANCEMENT; CANCER TUMOR-SUPPRESSOR; REPLICATION PROTEIN-A; HOMOLOGOUS RECOMBINATION; SACCHAROMYCES-CEREVISIAE; MAMMALIAN-CELLS; COMPLEX; REPAIR; PROMOTES |
| Popis | Central to homologous recombination in eukaryotes is the RAD51 recombinase, which forms helical nucleoprotein filaments on single-stranded DNA (ssDNA) and catalyzes strand invasion with homologous duplex DNA. Various regulatory proteins assist this reaction including the RAD51 paralogs. We recently discovered that a RAD51 paralog complex from C. elegans, RFS-1/RIP-1, functions predominantly downstream of filament assembly by binding and remodeling RAD-51-ssDNA filaments to a conformation more proficient for strand exchange. Here, we demonstrate that RFS-1/RIP-1 acts by shutting down RAD-51 dissociation from ssDNA. Using stopped-flow experiments, we show that RFS-1/RIP-1 confers this dramatic stabilization by capping the 50 end of RAD-51-ssDNA filaments. Filament end capping propagates a stabilizing effect with a 5'-> 3' polarity approximately 40 nucleotides along individual filaments. Finally, we discover that filament capping and stabilization are dependent on nucleotide binding, but not hydrolysis by RFS-1/RIP-1. These data define the mechanism of RAD51 filament remodeling by RAD51 paralogs. |
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