PhD Dissertation Defense: Veysel Oğulcan Kaya, RELATIONSHIP BETWEEN UV-INDUCED DNE THREE-DIMENSIONAL STRUCTURE OF THE GENOME, Date & Time: 22 July, 2026 – 3:30 PM, Place: FENS L045

RELATIONSHIP BETWEEN UV-INDUCED DNA DAMAGE RESPONSE AND THE THREE-DIMENSIONAL STRUCTURE OF THE GENOME

Veysel Oğulcan Kaya

Molecular Biology, Genetics, and Bioengineering, PhD Dissertation, 2026

Thesis Jury

     Assoc. Prof. Ogün Adebali (Thesis Advisor)

  Assoc. Prof. Öznur Taştan

  Assoc. Prof. Nurcan Tunçbağ

Asst. Prof. Nur Mustafaoğlu

Asst. Prof. Eda Yıldırım

Date & Time: 22nd, July 2026 – 3.30 PM

Place: FENS L045

Keywords : 3D genome, nucleotide excision repair, UV irradiation, loop extrusion, chromatin organisation

Abstract

The human genome is folded into a three-dimensional (3D) hierarchy of compartments, topologically associating domains (TADs), and cohesin-extruded loops, an architecture that must remain navigable by the repair machinery. Ultraviolet (UV) radiation inflicts hundreds of thousands of helix-distorting photolesions, excised by nucleotide excision repair (NER), yet whether the 3D genome is a passive backdrop or an active participant has remained unclear. Time-resolved Hi-C of UV-irradiated human cells reveals that the damage response reorganises chromatin at every scale within minutes of exposure: contacts shift to shorter range, intra-compartment, especially A-A, interactions strengthen, and TAD boundaries are sharply reinforced. This reorganisation tracks repair, with the strongest, most accessible A-compartment domains excising cyclobutane pyrimidine dimers fastest and repair concentrated at boundaries and anchors. Combining profiling of repair-proficient and repair-deficient cells, including XPC^-/- and XPA^-/- cells with loop-extrusion simulations identifies two drivers: CTCF gained at boundaries captures cohesin at both anchors, favouring a fully extruded, insulated TAD, while lesion-stalled RNA polymerase II (RNAPII) and repair complexes shorten loops from within. These barriers counter the loop-lengthening of UV-induced transcriptional shutdown, and loop lengths predicted for each genotype are confirmed, marking the reorganisation as actively driven rather than incidental. The reinforced domains index damaged chromatin into smaller neighbourhoods that shorten repair-factor diffusion distances, favouring recognition and repair. Because this architectural response recurs across repair pathways, albeit at different scales, it appears to be an evolutionarily conserved strategy: the genome is not a passive scaffold but a dynamically folded substrate that transcription and repair jointly shape to protect its integrity.