DNA Repair Pathways for UV-Light-Induced Damage Ultraviolet (UV) light represents a major source of genomic instability, as its impact is DNA damage by physical means mainly in the form of thymine dimers. These dimers are formed by the covalent connection of two adjacent thymine bases, creating a disruption in helical structure that obstructs replication and transcription. Nature contains various mechanisms to repair such damage and ensure genomic stability, thereby avoiding the consequences of mutations that may have given raise to diseases such as cancer.
Key Repair Mechanisms
NER (Nucleotide Excision Repair)
NER plays a crucial role in removing classes of bulky DNA lesions that include CPDs and to 6-4PPs. This process includes cutting off a weakened part of the DNA strand and then creating an outlandish one using that residual template (Wikipedia contributors 12). NER efficiency is very different, for instance 6-4PPs are repaired faster than CPDs in mammalian cells1.
Photoreactivation:
This system uses a direct repair enzyme, photolyase that absorbs visible light to directly reverse the UV-induced damage. Photolyase however directly binds to CPDs and breaks the covalent bond between thymine bases, enabling them to be re-paired without excision 23. Such an efficient repair pathway has been retained in many organisms, which deserves to be pointed out.
Base Excision Repair (BER):
Base Excision Repair (BER): BER deals with the nonbulky lesions resulting from oxidative and more subtle modifications of individual DNA bases. Glycosylases recognize and cleave damaged bases, which are subsequently replaced selectively via insertion of specific DNA polymerase proteins (Fig. 23).UV DNA repair (ad) Though BER is not the major system for responding to UV damage, this pathway provides a complementation effect which contributes generally to genomic stability.
Challenges in Repair
Even with these impressive repair mechanisms, too much UV damage can override cellular repairs. For example, if multiple lesions are spatially close to each other in chromosomes or oncogenes having already accrued genetic defect DNA damage repair becomes very inefficient and irreparable. If the damage is too extensive to effectively repair, cells may choose apoptosis or senescence as a mean of preventing further spread of damaged DNA45. In this regard, genetic disorders such as xeroderma pigmentosum highlight the increased sensitivity to UV light and consequences of accumulated mutations resulting from defects in these repair pathways4.
Thus, overall the cells have good mechanisms but dependent on how they tolerate those damage at large levels before crossing over to acquire cancer genome. A better understanding of these processes should help to develop strategies to attenuate UV-related public health risks.
