DNA repair mechanisms protect our genome from carcinogenesis

Abstract

Human cells are constantly exposed to DNA damage. Without repair, damage can result in genetic instability and eventually cancer. The strong association between the lack of DNA damage repair, mutations and cancer is dramatically demonstrated by a number of cancer-prone human syndromes, such as xeroderma pigmentosum (XP), ataxia-telangiectasia (AT) and Fanconi anemia (FA). This review focuses on the historical discoveries related with these three diseases and describes their impact on the understanding of DNA repair mechanisms and the causes of human cancer. As deficiencies in DNA repair are also often related with progeria symptoms, unrepaired damage and aging are somehow related. Several other pathologies associated with DNA repair defects, genetic instability and increased cancer risk are also discussed. In fact, studies with cells from these many syndromes have helped in understanding important levels of protection against cancer and aging, although little help has actually been conferred to the patients in terms of therapy. Finally, the recent advances in combined basic and translational research on DNA repair and chemotherapy are presented.

Ageing as an Important Risk Factor for Cancer

“…It is also a significant aid for the prevention of serious, frequently fatal diseases, including cancer (43). DNA-repair activity seems to be attenuated during the course of ageing.…”

UVB-Induced Cell Death Signaling Is Associated with G1-S Progression and Transcription Inhibition in Primary Human Fibroblasts

“…The genes involved in complementation groups A, B, D, F and G are necessary for both NER sub-pathways, whereas XP-C and XP-E cells are deficient in GGR but proficient in TCR. The genes involved in the two complementation groups in the Cockayne Syndrome, viz., CS-A and CS-B, are required for TCR only [7], [8].…”

Recombinant Viral Vectors for Investigating DNA Damage Responses and Gene Therapy of Xeroderma Pigmentosum

“…Several libraries of viral vectors for the expression of small double-stranded RNA molecules (shRNA) targeting human genes are commercially available, and are already being used for understanding gene function. The use of such vectors to make cells deficient in more than one DNA repair pathway, using cells deficient in XP genes as hosts, for example, may help us to reveal the intricate network of interactions between the different metabolic pathways that contribute to genome maintenance after damage induction (Moraes, et al, 2011;in press). Moreover, the progress that has been made towards gene therapy for xeroderma pigmentosum, using these recombinant viral vectors is also discussed.…”