Chromatin Structure Following UV-Induced DNA Damage—Repair or Death?

Abstract

In eukaryotes, DNA is compacted into a complex structure known as chromatin. The unravelling of DNA is a crucial step in DNA repair, replication, transcription and recombination as this allows access to DNA for these processes. Failure to package DNA into the nucleosome, the individual unit of chromatin, can lead to genomic instability, driving a cell into apoptosis, senescence, or cellular proliferation. Ultraviolet (UV) radiation damage causes destabilisation of chromatin integrity. UV irradiation induces DNA damage such as photolesions and subjects the chromatin to substantial rearrangements, causing the arrest of transcription forks and cell cycle arrest. Highly conserved processes known as nucleotide and base excision repair (NER and BER) then begin to repair these lesions. However, if DNA repair fails, the cell may be forced into apoptosis. The modification of various histones as well as nucleosome remodelling via ATP-dependent chromatin remodelling complexes are required not only to repair these UV-induced DNA lesions, but also for apoptosis signalling. Histone modifications and nucleosome remodelling in response to UV also lead to the recruitment of various repair and pro-apoptotic proteins. Thus, the way in which a cell responds to UV irradiation via these modifications is important in determining its fate. Failure of these DNA damage response steps can lead to cellular proliferation and oncogenic development, causing skin cancer, hence these chromatin changes are critical for a proper response to UV-induced injury.

The Role of AKT/mTOR Pathway in Stress Response to UV-Irradiation: Implication in Skin Carcinogenesis by Regulation of Apoptosis, Autophagy and Senescence

“…Importantly, UV-induced photolesions not only predispose cells to mutational changes but also contribute to genomic instability due to defective replication and transcription. UV-induced photolesions distort DNA replication forks, thereby introducing double strand breaks (DSBs), which are generally sensed and processed via homologous recombination repair (HRR) and non-homologous end joining (NHEJ) [14]. …”

Chromatin Remodeling in Nucleotide Excision Repair in Mammalian Cells

“…At this initial step, in TCR CSA and CSB direct the basic repair machinery to RNA polymerase II stalled at the lesion [28]. On the other hand, in GGR damage site recognition is carried out by XPC-hHR23B and UV-DDB/XPE complexes [13,25,[29][30][31]. The defect in one of the NER proteins is the consequence of three rare recessive syndromes: Xeroderma pigmentosum (XP), Cockayne syndrome (CS) and the photosensitive brittle hair disorder trichothiodystrophy (TTD) [26,31,32].…”

“…One of the most common environmental stresses that produce lesions in DNA is UV light. UVC irradiation induces cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts (6-4PP) which result in an abnormal DNA structure that signals the lesion [7], [13][14][15]. However, they can be distributed differently along the chromatin structure.…”

The UV-C Induced Cell Death in Human Malignant Melanoma and Normal Fibroblasts

“…When the repair is not successful, cells can undergo some kind of cell death. The severe damage cause that the affected cells suffer necrosis or they undergo apoptosis [1,2]. Interestingly, fragmentation of DNA, meaning high frequency of DNA double strand breaks (DSBs), is a characteristic feature for both apoptosis and necrosis processes.…”