Hydrogen bonds play at best only a peripheral role in the accurate pairing of DNA bases, researchers have shown, overturning the conventional wisdom long been held by biochemists. The finding represents a milestone in researchers' understanding of the workings of DNA -- the genetic bedrock of all organisms -- and forces scientists back to the drawing board to revisit the fundamental question of what's really behind the amazing fidelity of DNA replication.
Eric Kool, the University of Rochester professor of chemistry who led the study reported in the September 30 issue of the Proceedings of the National Academy of Science, suggests that it's now more likely than ever that the distinctive shapes and sizes of each of the four DNA bases underpin the impressive 99.99-percent accuracy of DNA replication. Like a space in a jigsaw puzzle that can be filled only by the one piece with a matching shape, only one base is capable of squeezing into a DNA strand opposite any given partner.
"The apparently inescapable conclusion is that H-bonds are not absolutely required," agrees Myron Goodman, a biologist and DNA expert from the University of Southern California, in a PNAS analysis accompanying Kool's paper. "These results provide an impetus to consider what role H- bonds actually play in stabilizing DNA and enhancing DNA polymerase fidelity. ... The notion that H-bonds alone keep the two strands of a DNA double helix together, found in many textbooks, seems inadequate."
The conclusion is based upon the finding that growing strands of DNA can accurately incorporate a nucleotide that closely resembles the DNA base thymine but lacks the natural base's ability to form hydrogen bonds.
The findings build upon earlier work by Kool that
showed that when thymine is replaced in a DNA template by
difluorotoluene, a ring-like molecule that very closely
mimics thymine's shape but can't form hydrogen bonds, DNA-
Contact: Stephen Bradt
University of Rochester