The inability to disassemble Rad51 nucleoprotein filaments leads to aberrant mitosis and cell death

Tadas Andriuskevicius, Anton Dubenko, Svetlana Makovets*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The proper maintenance of genetic material is essential for the survival of living organisms. One of the main safeguards of genome stability is homologous recombination involved in the faithful repair of DNA double-strand breaks, the restoration of collapsed replication forks, and the bypass of replication barriers. Homologous recombination relies on the formation of Rad51 nucleoprotein filaments which are responsible for the homology-based interactions between DNA strands. Here, we demonstrate that without the regulation of these filaments by Srs2 and Rad54, which are known to remove Rad51 from single-stranded and double-stranded DNA, respectively, the filaments strongly inhibit damage-associated DNA synthesis during DNA repair. Furthermore, this regulation is essential for cell survival under normal growth conditions, as in the srs2Δ rad54Δ mutants, unregulated Rad51 nucleoprotein filaments cause activation of the DNA damage checkpoint, formation of mitotic bridges, and loss of genetic material. These genome instability features may stem from the problems at stalled replication forks as the lack of Srs2 and Rad54 in the presence of Rad51 nucleoprotein filaments impedes cell recovery from replication stress. This study demonstrates that the timely and efficient disassembly of recombination machinery is essential for genome maintenance and cell survival.

Original languageEnglish
Article number1450
Number of pages25
JournalBiomedicines
Volume11
Issue number5
Early online date15 May 2023
DOIs
Publication statusPublished - 15 May 2023

Keywords / Materials (for Non-textual outputs)

  • budding yeast
  • mitotic bridges
  • Rad51 nucleoprotein filament disassembly
  • Rad54 and Srs2
  • stalled replication forks

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