利用纳米孔探测DNA损伤情况

Scientists worldwide are racing¹ to sequence DNA² -- decipher（解密） genetic⁴ blueprints⁶ -- faster and cheaper than ever by passing strands⁷ of the genetic material through molecule-sized pores. Now, University of Utah scientists have adapted this "nanopore" method to find DNA damage that can lead to mutations and disease. The chemists report the advance in the week of June 18 online edition of the journal Proceedings⁹ of the National Academy of Sciences.

"We're using this technique and synthetic¹⁰ organic chemistry to be able to see a damage site as it flies through the nanopore," says Henry White, distinguished¹¹ professor and chair of chemistry at the University of Utah and senior coauthor of the new study.

Strands of DNA are made of "nucleotide（核苷酸） bases" known as A, T, G and C. Some stretches of DNA strands are genes¹².

The new method looks for places where a base is missing, known as an "abasic site," one of the most frequent forms of damage in the 3-billion-base human genome or genetic blueprint⁵. This kind of DNA damage happens 18,000 times a day in a typical cell as we are exposed to everything from sunlight to car exhaust. Most of the damage is repaired, but sometimes it leads to a gene³ mutation⁸ and ultimately disease.

By combining nanopore damage-detection with other chemical ways of altering DNA, the researchers hope to make this new technique capable of detecting other kinds of DNA damage by converting the damage to a missing base, says the study's other senior coauthor, Cynthia Burrows¹³, a distinguished professor of chemistry at the University of Utah.

She adds: "Damage to the bases of DNA contributes to many age-related diseases, including melanoma（黑素瘤） ; lung, colon¹⁴ and breast cancers; Huntington's disease; and atherosclerosis（动脉粥样硬化） ."

A patent is pending¹⁵ on the new method of doing chemistry on DNA that allows damage sites to be found using nanopore technology.

White and Burrows conducted the study with first author, Na An, a doctoral student in chemistry and Aaron Fleming, a postdoctoral research associate in chemistry. The study was funded by the National Institutes of Health, with equipment and software donations by Electronic BioSciences of San Diego.