Navigating nuclear space: How Rad51 filaments promote long-range homology search during homologous recombination – Lessons from budding yeast
Abstract
DNA double-strand breaks (DSBs) threaten genomic integrity, with erroneous repair leading to chromosomal rearrangements and pathologies. In eukaryotes, DSBs are primarily repaired via non-homologous end-joining (NHEJ) or homologous recombination (HR). HR restores genetic information by using an undamaged homologous sequence as a template, a process dependent on Rad51-mediated homology search. This review synthesizes recent advances in our understanding of HR, with a focus on the homology search process in mitotic cells, primarily using Saccharomyces cerevisiae as a model organism. We explore factors that limit recombination efficiency and discuss how Rad51 filament dynamics overcome spatial and temporal challenges imposed by nuclear architecture and chromatin dynamics, to ensure efficient HR. Key insights include the dynamic behavior of Rad51 filaments, which undergo cycles of compaction and extension, thereby optimizing exploration of the nuclear volume and increasing the likelihood of encountering distant homologous sequences. The interplay between long-range resection, filament elongation, and nuclear constraints further shapes the search process, balancing the need for extensive exploration with the risks of excessive DNA degradation and ectopic recombination. Collectively, these findings support an integrated model in which the efficiency and accuracy of homologous recombination are governed by regulated Rad51 filament dynamics and the constraints imposed by nuclear architecture.
Related
- The 7SK small nuclear ribonucleoprotein links the cell responses to transcription and replication stress by promoting replication fork reversal and homologous recombination
- m7G modification in mRNA cooperates with QKI to promote homologous recombination repair
- Structures and molecular mechanisms of RAD54B in modulating homologous recombination
- DTX3 Suppresses the NPM3-RUVBL1 Axis to Inhibit Homologous Recombination Repair and Abrogate Tumor Radioresistance.
- Role of calcineurin B homologous protein 3 in C2C12 myogenic differentiation
BibTeX
@article{lakhal2026navigating,
title = {{Navigating nuclear space: How Rad51 filaments promote long-range homology search during homologous recombination – Lessons from budding yeast}},
author = {Fadma Lakhal and Angela Taddei},
journal = {DNA Repair},
year = {2026},
month = aug,
doi = {10.1016/j.dnarep.2026.103954},
url = {https://hal.science/hal-05840606v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Navigating nuclear space: How Rad51 filaments promote long-range homology search during homologous recombination – Lessons from budding yeast
AU - Fadma Lakhal
AU - Angela Taddei
PY - 2026
DA - 2026/08/05
JO - DNA Repair
DO - 10.1016/j.dnarep.2026.103954
UR - https://hal.science/hal-05840606v1
AB - DNA double-strand breaks (DSBs) threaten genomic integrity, with erroneous repair leading to chromosomal rearrangements and pathologies. In eukaryotes, DSBs are primarily repaired via non-homologous end-joining (NHEJ) or homologous recombination (HR). HR restores genetic information by using an undamaged homologous sequence as a template, a process dependent on Rad51-mediated homology search. This review synthesizes recent advances in our understanding of HR, with a focus on the homology search process in mitotic cells, primarily using Saccharomyces cerevisiae as a model organism. We explore factors that limit recombination efficiency and discuss how Rad51 filament dynamics overcome spatial and temporal challenges imposed by nuclear architecture and chromatin dynamics, to ensure efficient HR. Key insights include the dynamic behavior of Rad51 filaments, which undergo cycles of compaction and extension, thereby optimizing exploration of the nuclear volume and increasing the likelihood of encountering distant homologous sequences. The interplay between long-range resection, filament elongation, and nuclear constraints further shapes the search process, balancing the need for extensive exploration with the risks of excessive DNA degradation and ectopic recombination. Collectively, these findings support an integrated model in which the efficiency and accuracy of homologous recombination are governed by regulated Rad51 filament dynamics and the constraints imposed by nuclear architecture.
SN - 1568-7864
SN - 1568-7856
ER -