 |
| Schematic
of different mechanisms of DNA
damage. |
Ionizing radiation, chemicals, and
other agents can result in genetic
damage, which, if not repaired, can
lead to diseases such as cancer. Fortunately,
a system of genes directs the production
of sensitive DNA repair enzymes, which
monitor for genetic damage and fix
most errors. The role of DNA repair
processes in fixing genetic damage,
as well as the role of genetically
impaired repair mechanisms in cancer,
were first discovered by investigators
funded by predecessors to the Office
of Science in the 1960s. More recently
at Lawrence Livermore, Los Alamos,
and Lawrence Berkeley national laboratories,
researchers have cloned and studied
a number of crucial DNA repair genes.
A clear picture is emerging that unrepaired
DNA damage is the culprit in the long-term
consequences of radiation exposure.
Scientists now see that X-rays, ultraviolet
light, and cancer-causing chemicals
work in similar ways in disabling
the natural DNA repair mechanisms.
A team at Lawrence Berkeley demonstrated
a strong correlation between the inability
to repair oxidative damage to DNA
and severe developmental failure and
early death in a hereditary condition
called Cockayne's syndrome.
Scientific Impact:
Research on DNA repair helps scientists
better understand biological processes,
from the microscale (e.g., cell death)
to the macroscale (e.g., evolution).
So central is the role of DNA repair
that in 1994, Science magazine
designated the entire class of DNA
repair enzymes as "Molecule of the
Year."
Social Impact: By
explaining how DNA repair processes
can go awry, scientists contribute
to sound policymaking on environmental
hazards. This research also could
lead to medical and pharmaceutical
treatments for repair-deficiency disorders,
implicated in conditions ranging from
cancer to aging.
Reference: R.D.
Wood, M. Mitchell, J. Sgouros, T.
Lindahl, "Human DNA Repair Genes,"
Science 291 (2001) 1284-1289.
L.H. Thompson, D. Schild, "The contribution
of homologous recombination in preserving
genome integrity in mammalian cells,"
Biochimie (1999) 87-105.
M. Takata, M.S. Sasaki, S. Tachiiri,
T. Fukushima, E. Sonoda, D. Schild,
L.H. Thompson, S. Takeda, "Chromosome
instability and defective recombinational
repair in knockout mutants of the
five Rad51 paralogs," Mol. Cell.
Biol. 21 (2001) 2858-2866.
Le Page, F., Kwoh, E.E., Avrutskaya,
A., Gentil, A., Leadon, S.A., Sarasin,
A., and Cooper, P.K. "Transcription-Coupled
Repair of 8-oxoGuanine: Requirement
for XPG, TFIIH, and CSB and Implications
for Cockayne Syndrome," Cell
101, 159-171 (2000).
Brenneman, M. A., A. E. Weiss, J.
A. Nickoloff and D. J. Chen, "XRCC3
is Required for efficient repair of
chromosome break by homologous recombination,"
DNA Repair Mutat Res 20;459(2):89-97
(2000).
URL:
http://dir.niehs.nih.gov/dirlmg/DNArepair.html
Technical Contact:
Dr. David Thomassen, Life Sciences
Division, Office of Biological and
Environmental Research, 301-903-9817
Press Contact: Jeff
Sherwood, DOE Office of Public Affairs,
202-586-5806
SC-Funding Office:
Office of Biological and Environmental
Research |
