Thesis

Ctf8

Small subunit of the Ctf18-RFC alternative clamp loader; helps load or regulate PCNA during replication-associated sister chromatid cohesion.

TONSL-MMS22L

DNA repair complex targeted to newly replicated chromatin by the ankyrin-repeat domain of TONSL, which recognizes H4K20me0 on newly deposited H4. This directs repair activity to regions where a sister chromatid is available as a homologous template

Dcc1

Ctf18-RFC subunit that works with Ctf8 and Ctf18; important for replisome-associated PCNA loading and cohesion establishment.

IDCL of PCNA

The interdomain connecting loop of PCNA; a major binding surface for PIP-box-containing proteins.

PCNA C-face

The face of PCNA oriented toward newly synthesized DNA and often associated with polymerase or repair-factor binding.

PCNA N-face

The opposite face of PCNA away from polymerase; orientation matters because different factors bind PCNA asymmetrically at the replication fork.

Hus1

Component of the 9-1-1 checkpoint clamp with Rad9 and Rad1; loaded at DNA damage sites to activate ATR signaling.

Exo1

5′ to 3′ exonuclease involved in mismatch repair, resection, Okazaki fragment processing, and some double-strand break repair pathways.

RNaseH

Enzyme that removes RNA from RNA-DNA hybrids; important for removing RNA primers and resolving R-loops.

Pol η

Translesion synthesis polymerase specialized for bypassing UV-induced thymine dimers with relatively low mutagenesis

Pol ι

Error-prone translesion polymerase with unusual template preferences; helps bypass certain DNA lesions.

Pol κ

Translesion polymerase involved in bypassing bulky adducts and some replication-blocking lesions.

Pol ζ

Extender polymerase in translesion synthesis; often extends from distorted primer termini after another TLS polymerase inserts across a lesion.

Rev1

TLS scaffold protein and deoxycytidyl transferase; recruits and coordinates Pol ζ and other TLS polymerases at damaged DNA.

MSH2–MSH6 / MutSα

Mismatch repair complex that recognizes base-base mismatches and small insertion/deletion loops.

MSH2–MSH3 / MutSβ

Mismatch repair complex that recognizes larger insertion/deletion loops.

MutLα

Mismatch repair complex, usually MLH1–PMS2 in humans; acts downstream of MutS complexes to coordinate excision and repair.

DNMT1

Maintenance DNA methyltransferase that copies CpG methylation patterns onto the newly synthesized daughter strand after replication.

Pol β

Gap-filling polymerase in base excision repair; inserts nucleotides after damaged bases are removed.

XRCC1–Ligase III

Base excision repair scaffold-ligation complex; X organizes repair factors and Y seals repaired DNA nicks.

AP endonuclease

Cuts DNA at abasic sites during base excision repair, creating an entry point for Pol β-mediated repair.

PIP degron

PCNA-binding degradation motif that targets certain replication factors for CRL4-dependent ubiquitination after they bind chromatin-loaded PCNA.

p21

CDK inhibitor that binds PCNA through a high-affinity PIP-box and can block PCNA-dependent DNA replication or repair factor recruitment.

Clr4

Cullin-RING E3 ligase family that ubiquitinates chromatin-bound replication factors, often through substrate receptors such as Cdt2.

Cdt1

Replication licensing factor that helps load MCM helicase onto origins in G1; degraded or inhibited after S phase begins to prevent rereplication.

Rad6–Rad18

E2–E3 ubiquitin system that monoubiquitinates PCNA after replication stress, promoting translesion synthesis.

Ubc13–Mms2–Rad5

Error-free damage tolerance machinery that extends PCNA ubiquitin chains, promoting template switching rather than TLS.

ATR kinase

Master replication-stress checkpoint kinase activated by RPA-coated ssDNA and the 9-1-1 clamp; stabilizes stalled forks and delays cell-cycle progression.

ATM kinase

DNA damage checkpoint kinase primarily activated by double-strand breaks; coordinates repair, checkpoint signaling, and apoptosis when damage is severe.

ATAD5/Elg1-RFC

Alternative RFC complex that unloads PCNA from chromatin after replication and repair.

Rad17-RFC

Checkpoint clamp loader that loads the 9-1-1 clamp at DNA damage or stalled fork structures.

9-1-1 clamp

Rad9–Rad1–Hus1 checkpoint clamp that resembles PCNA but functions mainly in ATR checkpoint activation.

Chk1

Downstream ATR effector kinase that suppresses origin firing, stabilizes forks, and delays cell-cycle progression.

Rad5 / HLTF / SHPRH

E3 ligase/remodeler family involved in PCNA polyubiquitination and template switching.

CAF-1

Histone chaperone that deposits new H3-H4 onto replicated DNA through PCNA-dependent recruitment.

ASF1

H3-H4 histone chaperone that hands newly synthesized histones to CAF-1 and supports replication-coupled nucleosome assembly.

FANCJ

DNA helicase involved in resolving G-quadruplexes and supporting replication through difficult templates.

PCNA SUMOlyation

Modification that recruits anti-recombinogenic factors such as Srs2 in budding yeast.

PCNA ubiquitylation

Damage-induced modification of PCNA that regulates translesion synthesis and template switching.

Hydroxyurea

Ribonucleotide reductase inhibitor that depletes dNTP pools and stalls replication forks.

Aphidicolin

DNA polymerase inhibitor that induces replication stress by slowing replicative polymerases.

Camptothecin

Topoisomerase I poison that creates replication-associated single-ended DSBs.

SMARCAL1

DNA translocase that promotes fork reversal at stalled forks.

HLTF

E3 ubiquitin ligase and translocase involved in PCNA polyubiquitination and fork reversal/template switching.

ZRANB3

PCNA-interacting translocase involved in fork remodeling and replication stress responses.

OGG1

Glycosylase that removes 8-oxoG paired with cytosine.

MUTYH

Glycosylase that removes adenine mispaired with 8-oxoG.

Rad51

Recombinase that forms nucleoprotein filaments on ssDNA and catalyzes homology search and strand invasion.

BRCA2

RAD51 mediator that loads RAD51 onto ssDNA and promotes filament formation.

Fanconi anemia pathway

DNA repair network essential for replication-coupled interstrand crosslink repair

FANCD2-FANCI

Central Fanconi complex that becomes monoubiquitinated and recruits downstream repair nucleases.

FA core complex

E3 ligase machinery that monoubiquitinates FANCD2-FANCI

SLX4

Scaffold that recruits structure-specific nucleases during crosslink repair.

XPF-ERCC1 in ICL repair

Nuclease that helps unhook interstrand crosslinks.

Rad6-Rad18

E2-E3 pair that monoubiquitinates PCNA after replication-blocking damage.

H3K27me3

Polycomb-associated repressive mark deposited by PRC2.

H3K36me3

Histone mark enriched over transcribed gene bodies; linked to transcription elongation and repair pathway choice.

H3K27ac

Active enhancer and promoter mark deposited by acetyltransferases such as p300/CBP.

γH2AX

Phosphorylated H2AX surrounding DSBs; platform for DNA damage response factor accumulation.

CRL2^LRR1

A metazoan E3 ubiquitin ligase (CUL2, RBX1, Elongin B/C, LRR1) that ubiquitinates MCM7 to promote CMG unloading at replication termination.

SCF^Dia2

A budding yeast E3 ubiquitin ligase (Cdc53, Hrt1, Skp1, Dia2) that ubiquitinates MCM7 to promote CMG unloading at replication termination.

Werner helicase (WRN)

A RecQ-family DNA helicase with 3′→5′ helicase and exonuclease activities that maintains genome stability by resolving DNA structures during replication, repair, and telomere maintenance. Mutations cause Werner syndrome, a premature-aging disorder.

XPC–RAD23B

Damage recognition complex in global-genome NER (GG-NER) that detects helix-distorting DNA lesions and recruits TFIIH.

CSA and CSB

Transcription-coupled NER (TC-NER) factors that recognize and respond to RNA polymerase II stalled at DNA lesions.

TFIIH

Multiprotein complex containing XPB and XPD ATP-dependent DNA translocase/helicase activities that opens DNA around the lesion and verifies damage.

XPF–ERCC1

Structure-specific endonuclease that cuts the damaged DNA strand 5′ of the lesion.

XPA

DNA damage verification and scaffolding protein that organizes the NER pre-incision complex.

XPG

Structure-specific endonuclease that cuts the damaged DNA strand 3′ of the lesion.

Bloom helicase

A 3′→5′ RecQ-family DNA helicase that maintains genome stability by resolving recombination intermediates and stalled replication forks. Forms the BTR complex with TOP3A–RMI1–RMI2 to dissolve double Holliday junctions, preventing crossover recombination. Mutations cause Bloom syndrome, characterized by elevated sister chromatid exchange and cancer predisposition.

Pif1

A conserved 5′→3′ DNA helicase that resolves G-quadruplexes, unwinds DNA–RNA hybrids, and promotes replication through difficult DNA regions. It also facilitates Okazaki fragment processing and inhibits telomerase-mediated telomere elongation.

Ku70–Ku80 (XRCC6–XRCC5)

Ring-shaped heterodimer that recognizes and encircles DNA double-strand break ends, protecting them from resection and recruiting DNA-PKcs.

DNA-PKcs (PRKDC)

DNA-dependent protein kinase that associates with Ku-bound DNA ends to form DNA-PK, coordinating end synapsis and processing through phosphorylation of repair factors.

Artemis (DCLRE1C)

Structure-specific nuclease activated by DNA-PKcs that processes incompatible DNA ends by trimming overhangs and opening DNA hairpins.

XRCC4

Structural scaffolding protein that binds and stabilizes DNA ligase IV, supporting the alignment and ligation of DNA ends.

DNA ligase IV (LIG4)

ATP-dependent DNA ligase responsible for sealing DNA double-strand breaks during c-NHEJ.

XLF (NHEJ1/Cernunnos)

XRCC4-like protein that promotes DNA end synapsis and stabilizes the ligation machinery, partly through XRCC4–XLF filament formation.

Polymerase μ (POLM)

X-family DNA polymerase that fills short gaps at DNA ends, including poorly paired or noncomplementary ends.

Polymerase λ (POLL)

X-family DNA polymerase that fills gaps at partially complementary DNA ends before ligation.

PAXX

Ku-interacting protein that stabilizes DNA end joining and supports NHEJ, particularly when other end-synapsis factors are compromised.

53BP1

DNA damage response protein that promotes NHEJ by limiting DNA end resection, favoring end joining over homologous recombination.

Shieldin complex (SHLD1, SHLD2, SHLD3, REV7)

Downstream effector of 53BP1–RIF1 that limits end resection and promotes NHEJ.

APLF

DNA repair factor that interacts with Ku and XRCC4–Ligase IV, facilitating assembly of NHEJ complexes at DNA breaks.

MRN complex (MRE11–RAD50–NBS1)

DNA double-strand break sensor and processing complex that recruits and activates ATM kinase and initiates DNA end resection for homologous recombination. MRE11 provides nuclease activity, RAD50 provides ATP-dependent DNA tethering, and NBS1 coordinates DNA damage signaling and repair factor recruitment

Break-induced replication (BIR)

A homologous recombination-mediated DNA repair pathway that repairs one-ended double-strand breaks, such as those caused by collapsed replication forks. Following end resection and RAD51-mediated strand invasion, a new replication fork is established that synthesizes DNA over long distances, often through a migrating D-loop. BIR is frequently associated with conservative DNA synthesis and increased mutagenesis.

MRX complex

The budding yeast counterpart of the mammalian MRN complex that recognizes and tethers DNA double-strand breaks, initiates DNA end resection, and activates DNA damage signaling. Mre11 provides nuclease activity, Rad50 mediates ATP-dependent DNA tethering, and Xrs2 recruits signaling and repair factors, including Tel1 (ATM homolog).x

DNA2–STR–RPA complex

budding yeast DNA end-resection machinery that processes double-strand breaks during homologous recombination. Sgs1 unwinds DNA, Dna2 degrades the 5′ strand, RPA stabilizes the exposed 3′ ssDNA, and Top3–Rmi1 supports Sgs1 activity.

BTR complex (BLM–TOP3A–RMI1–RMI2)

The human counterpart of the yeast STR complex that dissolves double Holliday junctions to produce non-crossover recombination products. BLM unwinds recombination intermediates, TOP3A decatenates DNA strands, and RMI1–RMI2 stabilizes and stimulates the complex.

STR complex (Sgs1–Top3–Rmi1)

A budding yeast DNA repair complex that dissolves double Holliday junctions during homologous recombination, preventing crossover formation and sister chromatid exchange. Sgs1 is a 3′→5′ RecQ helicase, Top3 is a type IA topoisomerase, and Rmi1 stimulates and stabilizes the complex. The human equivalent is the BTR complex (BLM–TOP3A–RMI1–RMI2).

Rad52

A homologous recombination protein that binds ssDNA and promotes annealing between complementary DNA strands. In budding yeast, X also mediates RAD51 loading onto RPA-coated ssDNA. In humans, X is particularly important for RAD51-independent repair pathways, including single-strand annealing (SSA), break-induced replication (BIR), and mitotic DNA synthesis (MiDAS). BRCA2 in humans.

COMPASS (Complex of Proteins Associated with Set1)

A SET1-containing histone methyltransferase complex that methylates H3K4, a mark associated with active promoters and transcription. In mammals, related complexes contain SETD1A/B or MLL/KMT2 enzymes.

SAGA (Spt–Ada–Gcn5 Acetyltransferase)

A transcriptional coactivator complex containing GCN5/KAT2A histone acetyltransferase and a deubiquitination module (USP22 in humans). Acetylates histone H3 and removes H2B ubiquitination to regulate transcription.

NuRD (Nucleosome Remodeling and Deacetylase)

A chromatin-regulating complex combining CHD3/4 ATP-dependent nucleosome remodeling with HDAC1/2 histone deacetylation. Regulates transcriptional repression, differentiation, and chromatin accessibility.

PRC1 (Polycomb Repressive Complex 1)

A transcriptional silencing complex containing RING1A/B E3 ubiquitin ligase activity that monoubiquitinates histone H2A at K119, promoting Polycomb-mediated repression.

PRC2 (Polycomb Repressive Complex 2)

An EZH1/2-containing histone methyltransferase complex that deposits H3K27me2/3, establishing repressive chromatin domains and maintaining developmental gene silencing.

NSD family complexes (NSD1/2/3)

SET-domain histone methyltransferases that predominantly deposit H3K36me2, regulating chromatin organization, transcription, and antagonism of inappropriate PRC2 activity.

DOT1L complex

A histone methyltransferase assembly that methylates H3K79 within the histone globular domain, linking nucleosome modification to transcriptional regulation and elongation.

SWI/SNF (BAF/PBAF)

BRG1/SMARCA4- or BRM/SMARCA2-containing ATP-dependent chromatin remodeling complexes that reposition or evict nucleosomes to regulate DNA accessibility, transcription, and differentiation.

ISWI complexes (ACF, CHRAC, NURF)

ATP-dependent remodelers containing SMARCA5/SNF2H or SMARCA1/SNF2L that slide and space nucleosomes to organize chromatin and regulate transcription.

SWR1 complex (SRCAP/p400 in mammals)

An ATP-dependent histone-exchange complex that replaces canonical H2A–H2B dimers with H2A.Z–H2B dimers, regulating promoter chromatin architecture and transcription.

HIRA complex

A histone chaperone complex containing HIRA, UBN1/2, and CABIN1 that deposits the histone variant H3.3 independently of DNA replication, particularly at actively transcribed genes.