DNA Damage Response Mechanisms in Yeast Cells

The DNA damage response (DDR) in Saccharomyces cerevisiae encompasses a tightly regulated network that senses lesions, halts cell‐cycle progression and deploys specialised repair pathways to preserve genome integrity. Sensor kinases detect double‐strand breaks (DSBs) and single‐strand gaps, activating effector kinases that orchestrate cell‐cycle arrest and recruitment of repair factors. Homologous recombination (HR) predominates in the error‐free repair of DSBs, whereas non‐homologous end joining (NHEJ) provides a more rapid but potentially mutagenic alternative. Base excision repair (BER) corrects small base modifications and abasic sites, while mismatch repair (MMR) rectifies replication errors. During S phase, replication stress is alleviated by stabilising stalled forks, activating translesion DNA synthesis and coordinating replisome components to prevent fork collapse. Telomere maintenance and checkpoint recovery complete the cycle, ensuring that yeast cells resume proliferation only after successful genome restoration. As a model organism, budding yeast has illuminated conserved DDR components, from sensor kinases to polymerase subunits, offering insights into mechanisms of chromosome rearrangement, replication fidelity, oxidative stress defence and the maintenance of ageing‐related biomarkers.

Research from Nature Portfolio

Recent studies have elucidated how DSBs at natural inverted repeats can drive high‐frequency chromosome rearrangements through a DNA polymerase δ‐dependent process. Upon breakage, foldback annealing generates heterologous flaps that are trimmed by the polymerase’s proofreading activity. Subsequent fill‐in synthesis, reliant on the Pol32 subunit, produces hairpin‐capped ends that, when replicated, form dicentric chromosomes. Stabilisation of these aberrant structures involves non‐reciprocal telomere capture mediated by repeat sequences or centromere loss. This work advances our understanding of how DDR factors coordinate end processing and synthesis to influence genome architecture under conditions of compromised nuclease activity.

DNA Damage Response Mechanisms in Yeast Cells publication trend

The graph below shows the total number of articles in dna damage response mechanisms in yeast cells across all publications each year (not limited to Nature Index journals).

Technical terms

Double‐strand break (DSB): A lesion in which both DNA strands are severed, triggering checkpoint activation and specialised repair pathways.

Homologous recombination (HR): An error‐free repair mechanism that uses an undamaged sister chromatid as a template to restore DNA sequence at DSBs.

Non‐homologous end joining (NHEJ): A repair pathway that ligates broken DNA ends directly, often introducing small insertions or deletions.

Base excision repair (BER): A pathway that recognises and removes damaged bases or abasic sites, followed by DNA synthesis and ligation.

Replication stress: The slowing or stalling of replication forks due to DNA lesions, nucleotide depletion or protein obstacles, risking fork collapse.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can damage DNA, proteins and lipids, necessitating antioxidant defence.

Translesion DNA synthesis (TLS): A DNA damage tolerance process that uses specialised polymerases to bypass lesions at the cost of lower fidelity.

References

1. Double-strand breaks induce inverted duplication chromosome rearrangements by a DNA polymerase δ-dependent mechanism. Nature Communications (2023).
2. Mitochondrial superoxide dismutase Sod2 suppresses nuclear genome instability during oxidative stress. Genetics (2023).
3. Molecular Mechanisms of Resistance to Ionizing Radiation in S. cerevisiae and Its Relationship with Aging, Oxidative Stress, and Antioxidant Activity. Antioxidants (2023).
4. Genome Instability Induced by Low Levels of Replicative DNA Polymerases in Yeast. Genes (2018).