A high-resolution method maps DNA damage caused by smoking.

Researchers at the University of North Carolina School of Medicine have developed a high-resolution method for mapping DNA damage caused by smoking.
technology will help us better understand the risks of smoking and how it causes cancer, and why smokers are more likely to develop cancer, and even how these cancers are prevented.
study was published recently in PNAS.
link between smoking, DNA damage and lung cancer has been established for decades.
but determining the specific genes affected by smoking is still beyond our ability so far, largely because DNA is too small.
, a team of researchers at the University of North Carolina's (UNC) School of Medicine has found a way to solve the problem.
the study was led by Aziz Sancar, a professor of biochemistry and biophysics at UNC School of Medicine who won the 2015 Nobel Prize in Chemistry and focuses on the main carcinogen in tobacco, benzodiazepines (Bap).
team developed a way to map where the substance binds to DNA, by looking for which part of the genome was repaired after contact.
, smoking accounts for 30 percent of cancer deaths in the United States," said Sancar, a U.S. president.
we now have a genome-wide map of the damage caused by this substance.
would be great if the map raised awareness of the dangers of smoking.
if we know how to repair damaged DNA throughout the genome, it could also be helpful for drug developers, " he said.
" is notorious, But BaP is actually a very common substance.
it is a member of the hydrocarbon polycyclic aromatic hydrocarbon family, organic compound combustion, cold deep in outer space, will be this material.
fact, it's so common that in theory, it's also present on comets, and it helps with RNA synthesis, so life on Earth depends on it.
BaP was once a good thing for life, it caused serious environmental harm to complex organisms, " he said.
Because BaP is so common, organisms have evolved to cope with BaP pollution in the environment, such as forest fires, bonfire parties, and engines, but tobacco releases huge amounts of BaP (more than three times the amount of normal smoke) and goes straight into the lungs.
that in order to protect us from environmental hazards, our bodies break down toxic compounds into smaller molecules.
BaP breaks down into benzodiazepine (BPDE), which is more toxic.
BPDE is chemically combined with DNA and formed a very strong connection (addition) with ostrich, one of the four nucleotide bases.
is enough to alter DNA and make it unrecognizable, so affected cells cannot synthesize proteins or pass information on to future generations.
if the gene does not become a tumor suppressor gene, cancer will occur.
in laboratory have shown that even moderate doses of BaP can cause tumors to appear in mouse skin.
that is why BaP and BPDE from smoking are the leading causes of lung cancer.
DNA "formatted" to find out exactly where BaP was destroyed in the genome, the team applied some of the findings in the DNA repair process that led to Sancar winning the Nobel Prize in 2015.
specific proteins involved in the repair of nucleotide excision, they remove damaged DNA fragments, after which DNA synthases rebuild DNA fragments from a relative spiral.
impossible to look at the entire genome to determine where this process occurs.
so the researchers searched for fragments of damaged DNA in the cells, which were recovered during the repair process.
these fragments are chemically labeled, recovered, and sequenced.
put all these sequences together, the team mapped the location of DNA damaged and being damaged by smoking.
new method can be applied to any DNA damage associated with nucleotide removal repair," said Sancar.
" however, due to funding problems and the huge amount of work involved in DNA sequencing, the proof-of-concept map published by the team did not achieve the best resolution.
but the results suggest that mapping is feasible and can help people understand the relationship between disease and DNA damage.
in the future, they could also help find out which doses of a particular substance can exceed our innate ability to remove and repair nucleotides, which genes or genetic variants can help promote DNA repair, and whether certain locations are difficult to repair.
With this prototype map, the team was able to show that BPDE-related DNA repair occurs more often when the ostrich is next to the cytosine than when the bird is next to the thymus or adenine, suggesting that these areas are high-risk areas where BPDE causes mutations.
Sancar said: "I'm sure this information will give us a better understanding of why certain groups of people are more likely to develop cancer and who smoke-induced mutations that cause lung cancer."
Sancar also hopes that evidence that smoking can harm health at the cellular level will lead smokers to quit.
there are now more than 300 million smokers in China, more than 40 million smokers in the United States, and more than 1 billion smokers worldwide.
.