DNA molecules can adopt a variety of alternative structures. Among these structures are G-quadruplex DNA structures (G4s), which support cellular function by affecting transcription, translation, and telomere maintenance. These structures can also induce genome instability by stalling replication, increasing DNA damage, and recombination events. G-quadruplex-driven genome instability is connected to tumorigenesis and other genetic disorders. In recent years, the connection between genome stability, DNA repair and G4 formation was further underlined by the identification of multiple DNA repair proteins and ligands which bind and stabilize said G4 structures to block specific DNA repair pathways. The relevance of G4s for different DNA repair pathways is complex and depends on the repair pathway itself. G4 structures can induce DNA damage and block efficient DNA repair, but they can also support the activity and function of certain repair pathways. In this review, we highlight the roles and consequences of G4 DNA structures for DNA repair initiation, processing, and the efficiency of various DNA repair pathways.

Background/Objectives: Autophagy is a key degradative pathway involved in orthodontic tooth movement. DNA damage-regulated autophagy modulator 1 (DRAM1), a protein that plays a central role in the degradation of autophagic cargo, exhibits differential regulation in human periodontal ligament (hPDL) fibroblasts under compressive force. Single-nucleotide polymorphisms (SNPs) may influence force-induced gene expression. Therefore, this study investigated the impact of DRAM1 SNPs on its expression in hPDL fibroblasts under compression force. Methods: The hPDL sample comprised cells of 59 patients. A physiological compressive strain of 2 g/cm³ was used to simulate orthodontic tooth movement. Total RNA from hPDL fibroblasts was isolated to determine DRAM1 relative gene expression under loaded conditions and in a physiological control. Furthermore, a genotyping analysis of six SNPs within the DRAM1 gene (rs756534 (G/T), rs2138257 (C/T), rs2176092 (C/T), rs4622329 (A/G), rs10860812 (A/G), and rs4764657 (A/G)) was performed using real-time polymerase chain reaction. DRAM1 expression was com-pared among genotypes of each SNP using an alpha of 5%. Linear regression analysis was then employed to evaluate SNP-SNP interaction. Results: The relative DRAM1 gene expression was not statistically significantly different (p > 0.05) according to the geno-types. The SNP-SNP interaction did not demonstrate any statistically significant associ-ation either. Conclusions: DRAM1 gene expression in hPDL fibroblasts under orthodontic compression may not be regulated by the studied intronic SNPs in the gene encoding DRAM1.