DNA Damage and Repair
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
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.
Last Modified: July 17, 2012
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