Table 1 Endogenous and exogenous agents of replication stress^a,b

Endogenous Alternate DNA Structures

DNA-RNA hybrids (R-loops)^120,193

G-quadruplex DNA (stabilized by G4 ligand)^{194,195,196,197,198}

I-motif DNA (stabilized by I-motif ligand)^197,199

Telomere-specific DNA conformation (e.g., T-loop)^200,201

Reversed fork caused by reactive oxygen species (can be induced by replication inhibitor drug)²⁰²

DNA Damage Induced by Endogenous Biochemical Processes

DNA interstrand cross-links induced by reactive formaldehydes²⁰³

DNA-protein cross-links (can also be exogenously induced)^204,205,206

DNA Damage Induced by Radiation and Environmental Agents

Bulky DNA adducts (e.g., pyrimidine dimers) induced by ultraviolet light^207,208

Bulky DNA adducts induced by environmental DNA-damaging chemicals (e.g., polycyclic aromatic hydrocarbons)^209,210

DNA interstrand cross-links induced by exogenous agents (e.g., psoralen)²¹¹

DNA Damage Induced by Chemotherapy Drugs

Bulky DNA adducts (e.g., alkylated bases) induced by selected chemotherapeutic drugs^212,213

Replication Inhibition Caused by Chemotherapy Drugs

Drugs that cause nucleotide depletion (e.g., hydroxyurea)^214,215

Topoisomerase-binding compounds causing torsional stress (e.g., low dose camptothecin)^69,216

DNA polymerase inhibitors²¹⁷