Chemistry

Highly Reactive Abasic DNA

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Science  07 Mar 2014:
Vol. 343, Issue 6175, pp. 1058
DOI: 10.1126/science.343.6175.1058-c
CREDIT: N. E. PRICE ET AL., J. AM. CHEM. SOC. (7 FEBRUARY 2014) © 2014 AMERICAN CHEMICAL SOCIETY

The base on a DNA residue can be removed to leave an abasic site. This reaction can occur spontaneously, can be catalyzed enzymatically during certain repair processes, or can be induced by certain anticancer drugs and mutagens. The sugar of the abasic site can have two different structures that are in equilibrium: a cyclic hemiacetal form and a ring-opened form that bears an aldehyde group. Price et al. report that if the abasic site is opposite an adenine residue on double-stranded DNA, the aldehyde group of the ring-opened structure can react with the exocycle amino group of the adenine (the N6-amino group) and form a stable covalent cross-link. The formation of cross-links, which are among the most deleterious of DNA mutations, occurs in remarkably high yields, from 15 to 70% under physiologically relevant conditions, versus the 2 to 3% yield observed previously for similar reactions with guanine residues. This difference arises because the N6-amino group of adenine is positioned in the major groove for adenine but the corresponding N2-group of guanine is in the minor groove.

J. Am. Chem. Soc. 10.1021/ja410969x (2014).

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