Repair of DNA Damage Produced by Ionizing Radiation: A Minireview.
A knowledge of the biochemical and molecular basis of sensitivity to ionizing radiation can provide useful information regarding carcinogenesis, cancer susceptibility, and patient responses to radiotherapy. Various factors can influence radiosensitivity, including the induction, processing and manifestation of DNA damage. One factor known to strongly affect radiosensitivity is the ability of cells to repair damage to their DNA. Cells have evolved an elaborate array of enzymatic systems to maintain the integrity of their genetic material in the face of numerous agents that alter DNA structure or base sequence. Cellular repair of a macromolecule is known to occur only for DNA. In no other instance is the integrity of a single molecule so vital for the survival of a cell. A number of distinct enzymatic mechanisms are known that result in either the removal of damaged DNA bases or the rejoining of single- and double-strand breaks. In this article, we discuss some of the different types of DNA damage induced by ionizing radiation, including modified bases, sugar damage, strand breaks, and clustered DNA damage. This will be followed by a description of some of the basic mechanisms the cell uses to repair ionizing radiation-induced DNA damage, such as base excision repair. We will also discuss the relationship between DNA repair and other cellular processes, including transcription and the cell cycle. Recent advances, including the cloning and characterization of DNA repair genes implicated in human inherited disease, have provided new insights into the surprising complexity of cellular responses to DNA damage. Finally, the potential for using this information clinically will be discussed. The goal of this review is to inform the clinician not only about recent progress in the field of DNA repair, but also about relationships between the processing of DNA damage and other cellular functions.
Leadon
SA
Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA