Marcus S. Cooke talks with
ScienceWatch.com and answers a few questions about
this month's Emerging Research Front Paper in the field of
Molecular Biology & Genetics. The author has also
sent along an image of his work.
I think the paper is highly cited as it is a very comprehensive review that
covers three important, interrelated areas concerning oxidatively damaged
DNA. These are (i) mechanisms of formation; I was very happy that Miral
Dizdaroglu agreed to become a co-author, and he provided the expertise for
this section; (ii) effects of oxidatively damaged DNA at a cellular level;
Mark Evans, here at Leicester, wrote that section; and (iii) role of
oxidatively damaged DNA in disease; I wrote that section.
The breadth of the topic is a clear strength of the review, it stretches
from the description of events at the level of individual nucleobases, via
repair and mutation, to the possible role of such damage in
disease—right from conception, this was my plan for the review. It is
therefore very easy for authors to find information relevant to their
studies, and hence able to cite the review. I was very pleased that the
review was accepted in the Journal of the Federation of American
Societies for Experimental Biology(FASEB), which is a highly
read and prestigious journal, and certainly maximized the coverage that the
Does it describe a new discovery, methodology, or
synthesis of knowledge?
It is very much a synthesis of knowledge, not just a summary of literature.
Bringing the three areas (described above) together, I think, gives an
interesting, and useful perspective upon the importance of oxidatively
damaged DNA in health and disease. This is probably what made our review
attractive to FASEB J.
Too often I’ve heard reviews dismissed as being "something that
anyone can do." Yes, perhaps anyone can summarize the literature, but that
is not really a review. To my mind, a review should bring new ideas
together, in some novel way, or give new perspectives on existing data;
hence it should very much be a synthesis, not regurgitation.
Would you summarize the significance of your paper in
In layman's terms, this review summarizes the effects of damage to DNA, the
cell's blueprint, and how this damage might be involved in diseases, such
as cancer. It describes how highly reactive chemicals known as free
radicals, which can be generated by radiation, sunlight, and smoking, for
example, are constantly damaging DNA. Antioxidants help to prevent this
damage, and the DNA can also be repaired. However, if the antioxidants and
repair processes are overwhelmed, levels of damage increase, and this leads
to an increased risk of disease.
How did you become involved in this research, and were
there any particular problems encountered along the way?
Whilst studying on the MSc in Molecular Pathology and Toxicology, here at
Leicester, back in 1993, there was a lecture on free radicals. This grabbed
my interest, and I've pursued this field ever since.
Where do you see your research leading in the
Pretty much like the review, my research examines the effects of
oxidatively damaged DNA at a cellular level, but then translates those
findings into human studies, and vice versa. I see this continuing to be my
approach for the foreseeable future, but increasingly taking into account,
and understanding the basis of, interindividual variability.
Do you foresee any social or political implications for
There are social and political implications for any kind of medical
research. The fact that oxidatively damaged DNA is linked to so many
diseases, as highlighted in the review, makes it of profound importance.
Therefore society, via politics, needs to have the will to improve our
understanding of how this damage is formed, so we can develop intervention
strategies, and thereby reduce morbidity and mortality.
Dr. Marcus S. Cooke, Ph.D., FRCPath
Department of Cancer Studies and Department of Genetics
Radiation and Oxidative Stress Section
Robert Kilpatrick Clinical Sciences Building
University of Leicester
Reactive oxygen species: causes and consequences (from Cooke, MS. and
Evans, MD.  Science & Medicine, 10, #2, 98-111).
The production of reactive oxygen species (ROS) and reactive nitrogen
species (RNS) may arise from common exogenous and endogenous
processes. Free electrons produced by these processes are captured by
molecular oxygen to yield superoxide (O2•-). Further
interactions produce other reactive species, including the highly reactive
hydroxyl radicals (•OH) and HO-. (Mn+/M(n+1) are reduced and
oxidised metal ions, respectively.) Interaction of these reactive
species with nucleic acids may lead to a wide variety of nucleobase
products, deoxyribose products, strand breaks and DNA crosslinks.
Many of the modifications are substrates for DNA repair. However, a
consequence of unrepaired damage is, potentially, mutations which can lead
Click for a larger view.
KEYWORDS: BASE EXCISION-REPAIR; TRANSCRIPTION-COUPLED REPAIR;
COLI ENDONUCLEASE-III; SYSTEMIC-LUPUS-ERYTHEMATOSUS; RADICAL-INDUCED
FORMATION; CYTOSINE-DERIVED LESIONS; SINGLE-STRANDED-DNA; HUMAN
CELL-EXTRACTS; HUMAN MUTY HOMOLOG; ESCHERICHIA-COLI.