Yeast DNA Repair & Chromatin Dynamics

Overview

This project reviews Saccharomyces cerevisiae genes central to DNA damage response, homologous recombination, and chromatin remodeling. The 2024 research breakthrough using high-throughput 3D imaging revealed novel chromatin reconfiguration mechanisms during DNA repair, coupled with new understanding of histone recycling and FACT complex dynamics at the replication fork.

Key Research Areas

1. DNA Damage Recognition & Signaling - Sensor complexes and checkpoint control
2. Homologous Recombination (HR) - RAD51/52 filament formation and strand invasion
3. Double-Strand Break Repair - Resection, homology search, recombination
4. Chromatin Reconfiguration - Spatial reorganization following DNA damage
5. FACT Complex & Histone Dynamics - Histone recycling during replication/repair
6. Base Excision Repair (BER) - Single-strand break and oxidative damage repair
7. Mismatch Repair (MMR) - Replication error correction

Biological Significance

• Conservation - DNA repair mechanisms highly conserved; yeast reveals eukaryotic principles
• Structural biology - Cryo-EM revealing molecular mechanisms (FACT-replisome, nucleosome dynamics)
• Genomic stability - Central to preventing mutations and cancer
• Epigenetics - FACT and chromatin remodeling maintain epigenetic memory during repair
• Disease models - Defects in yeast homologs found in cancer and hereditary disorders

Project Goals

• Review genes central to DNA damage response and repair pathways
• Assess GO annotations for DNA repair, chromatin remodeling, and histone dynamics
• Identify genes at intersection of DNA repair and epigenetics
• Incorporate emerging structural biology insights (FACT-replisome complexes)
• Create reference for DNA repair and chromatin dynamics research

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STATUS

Last updated: 2025-12-30

Genes to Review

DNA Damage Sensing & Checkpoints

• [ ] RAD9 - 9-1-1 clamp (DNA damage sensor)
• [ ] CHK1 - Checkpoint kinase (rad53 homolog)
• [ ] DUN1 - Effector kinase (checkpoint signaling)

Homologous Recombination - Early Steps

• [ ] MRE11 - MRN complex (DNA end recognition, resection)
• [ ] RAD50 - MRN complex (DNA end tethering)
• [ ] XRS2 - MRN complex (nuclear localization)
• [ ] SAE2 - MRE11 cofactor (end processing)

Homologous Recombination - Core Machinery

• [ ] RAD51 - Recombinase (filament formation, strand invasion)
• [ ] RAD52 - RPA-RAD51 mediator (recombination intermediates)
• [ ] RAD54 - dsDNA translocase (chromatin remodeling for HR)
• [ ] RAD55 - RAD51 cofactor
• [ ] RAD57 - RAD51 cofactor

FACT Complex & Chromatin Remodeling at Replication/Repair

• [ ] SPT16 - FACT complex (histone chaperone, H2A/H2B transfer)
• [ ] POB3 - SSRP1 homolog (FACT complex partner)
• [ ] CHD1 - Chromatin remodeler
• [ ] SWI1 - SWI/SNF complex (chromatin remodeling)

Base Excision Repair

• [ ] RAD3 - Excision nuclease (transcription-coupled repair)
• [ ] REV3 - DNA polymerase ζ (translesion synthesis)
• [ ] DUN1 - Regulates dNTP pools during repair

Mismatch Repair

• [ ] MSH2 - MutS homolog (mismatch recognition)
• [ ] MSH6 - MutS homolog (mismatch specificity)
• [ ] MLH1 - MutL homolog (endonuclease licensing)
• [ ] PMS1 - MLH1 partner

General DNA Repair & Checkpoint Recovery

• [ ] RNR1 - Ribonucleotide reductase (dNTP synthesis)
• [ ] RNR2 - Ribonucleotide reductase (damage-inducible)
• [ ] RNR3 - Ribonucleotide reductase (damage-inducible)
• [ ] RNR4 - Ribonucleotide reductase (damage-inducible)

Progress

• Total genes: 28
• Reviewed: 0
• In progress: 0
• Completed: 0

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NOTES

2025-12-30

• Project initialized
• Focus: DNA damage response, homologous recombination, chromatin dynamics during repair
• Selected 28 genes spanning DNA sensing, HR machinery, FACT complex, BER, and MMR
• Emphasis on structural biology insights (FACT-replisome, histone recycling, chromatin reconfiguration)
• Ready to begin gene review workflow