The DNA-damage response in human biology and disease

Abstract

Cellular DNA is a sitting target for many toxic agents — from ionizing radiation to any number of chemicals in the environment. To that can be added errors that arise from physiological processes. Unchecked, damaged DNA can cause disease and threaten the gene pool. The human body has evolved several systems to detect DNA damage and mediate its repair. Stephen Jackson and Jiri Bartek review recent work on how DNA lesions are dealt with at the molecular level, and show how an understanding of DNA-damage responses is providing new avenues for disease management. The prime objective for every life form is to deliver its genetic material, intact and unchanged, to the next generation. This must be achieved despite constant assaults by endogenous and environmental agents on the DNA. To counter this threat, life has evolved several systems to detect DNA damage, signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management.