Biology Department Biology Department  

DNA Damage and Repair


DNA Damages (click to enlarge)

DNA Damage, Cellular Responses, and DNA Repair

In humans, DNA damage can result from exposure to environmental agents which include solar ultraviolet and ionizing radiation. DNA damage can increase the risk of developing adverse health effects and carcinogenesis over a lifetime. Prolonged exposures to solar ultraviolet radiation (UV light) may result in acute and chronic health effects on the skin, eye, and immune system. UV light affects many biological molecules including nucleic acids, producing both direct (e.g. pyrimidine dimers) and indirect (from free radicals and reactive oxygen species) damage to DNA.

Exposures to ionizing radiation (IR), e.g. x-rays, γ-rays and heavy ions may result in single- and double-stranded DNA breaks, damage to DNA bases, as well as more complex clusters of DNA damage. Of these, DNA double-stranded breaks are believed to be the most significant. Clustered damages are two or more lesions within about 10 base pairs (one helical turn), are especially difficult for cells to repair, and, if unrepaired or misrepaired, may result in double-stranded breaks. Research on the molecular mechanisms by which radiation produce cellular damage and by which cells respond and repair that damage are relevant to human health on earth and in space. New approaches to detecting clustered damage in people who encounter radiation through the low doses obtained from occupational exposure (airline flight crews, astronauts), from medical diagnostic procedures (PET, fluoroscopy, etc.) or from environmental sources are needed.

Space Radiation and the NSRL

A primary concern for space travel beyond earth orbit is exposure to galactic cosmic radiation (GCR) including protons and heavy ions. Acute exposures may result in death while prolonged exposures may increase cancer risk through several mechanisms including the induction of mutations and genome instability and modulation of the epigenome. Research in Biology and elsewhere is aimed at understanding the biological effects of GCR and developing countermeasures for harmful effects.

The National Space Radiation Laboratory (NSRL) is a unique user facility that provides ground-based access to the types of IR that are found in space beyond earth orbit. Biology Scientists support NASA funded researchers who come to Brookhaven to use the NSRL.

Brookhaven hosts the NASA Space Radiation Summer School.

Brookhaven is a member of the National Space Biomedical Research Institute (NSBRI) consortium.
The Low Dose Radiation Program

Humans may be exposed to low doses of Ionizing Radiation on earth from medical diagnostics, work at nuclear facilities, or legacy wastes from nuclear weapons programs. The goal of DOE’s Low Dose Radiation Program is to support research that will help determine health risks from exposures to low levels of Ionizing Radiation.

Human Skin Responses to Low Dose Radiation: Major radiation-induced DNA damages are complex lesion clusters; however, little is known of their induction, mechanisms of repair, or persistence in human tissue. Biology scientists focus on effects of low doses and dose rates of ionizing radiation vs. endogenous damages and their induction, repair, persistence, and possible bystander effects in human skin.

Cellular Responses and Epigenetic Effects: Cells possess complex signaling pathways that detect DNA damage, arrest cell cycle progression, modify chromatin, and induce repair systems or cell death. Using a high throughput DNA sequence-based approach and novel molecular reagents, Biology scientists are characterizing the mechanisms of transcriptional responses to exposures to low doses of IR as well as epigenetic changes that such exposures may produce.

 

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Last Modified: July 17, 2012
Please forward all questions about this site to: Kathy Folkers