Yeast DNA Repair & Chromatin Dynamics

Bottom line: in progress, with only the chromatin arm started. Budding yeast
repairs DNA through checkpoint signalling, homologous recombination, mismatch
repair and damage-tolerant polymerases, and every one of these steps has to
open and then restore chromatin. This project plans to review the GO
annotations of 26 distinct S. cerevisiae genes across those pathways
(DUN1 appears twice in the 27-line checklist). We picked the set to find where
DNA repair and chromatin handling meet, especially the FACT histone chaperone
and the remodelers. Four of the 26 now have reviews in the repo: SPT16 (54
annotation rows), POB3 (32), CHD1 (65) and SWI1 (40, plus one proposed NEW
term), with almost every row
accepted or kept as non-core and four removals in total. None of the
recombination, checkpoint, mismatch-repair or ribonucleotide-reductase genes
has a review folder, so the checklist below (whose stale footer says 28 genes,
0 reviewed) is out of date only for the chromatin genes.

Before the recombination work starts, several checklist labels need
correcting: in budding yeast the 9-1-1 clamp is Ddc1-Rad17-Mec3 and RAD9 is a
checkpoint adaptor, CHK1 is not the Rad53 homologue, and RAD3 (nucleotide
excision repair) and REV3 (translesion synthesis) are not base-excision-repair
genes.

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

Slides

• Slides (Marp source: YEAST_DNA_REPAIR_CHROMATIN-slides.md) — AI generated