PhD Dissertation: Cem Azgari, GENOME-WIDE ASSOCIATED OF REPAIR MECHANISMS WITH G-QUADRUPLEXES, Date & Time: 22 July, 2026 – 9:30 AM, Place: FENS L045
GENOME-WIDE ASSOCIATED OF REPAIR MECHANISMS WITH
G-QUADRUPLEXES
Cem Azgari
Molecular Biology, Genetics, and Bioengineering, PhD Dissertation, 2026
Thesis Jury
Assoc. Prof. Ogün Adebali (Thesis Advisor)
Asst. Prof. Alex Lyakhovich
Prof. Tunahan Çakır
Asst. Prof. Onur Öztaş
Asst. Prof. Nur Mustafaoğlu
Date & Time: 22nd, July 2026 – 9.30 AM
Place: FENS L045
Zoom Link: https://sabanciuniv.zoom.us/j/
Keywords: G-quadruplex, UV-induced DNA damage, nucleotide excision repair, Damage-seq, XR-seq
Abstract
G-quadruplexes (G4s) are secondary structures enriched at promoters and regulatory regions, where they are associated with transcriptional regulation, chromatin accessibility, and genome instability. However, how G4 regions respond to ultraviolet (UV)-induced DNA damage and nucleotide excision repair (NER) remains incompletely understood. This thesis presents a genome-wide analysis of the relationship between G4 formation, UV-induced cyclobutane pyrimidine dimer (CPD) and 6-4 photoproduct (6-4PP) formation, NER activity, chromatin context, transcriptional regulation, and mutation accumulation. First, a reproducible Snakemake workflow was developed to process Damage-seq and XR-seq datasets. Then, G4-Miner was applied to UV-induced time-series Hi-C data to infer G4 regions that formed, were lost, or remained persistent after UV exposure. Because these could not be confidently validated as UV-responsive G4 regions, analyses focused on experimentally defined HeLa-derived G4 regions. Damage-seq and XR-seq profiles, along with melanoma mutations, were analyzed using sequence-based simulations and matched-background comparisons to assess accessibility and transcription. Promoter-associated G4s were further evaluated by stratifying genes according to RNA Pol II occupancy and expression level. Finally, XGBoost models were used to identify whether chromatin, transcription factor, or histone marker features associated with damage, repair, and mutation signals. Together, the results show that G4 regions represent specialized regulatory genomic contexts where sequence composition, chromatin accessibility, transcription-associated strand asymmetry, UV lesion formation, repair activity, and mutation accumulation intersect.