Structural Basis of DNA Mispair Recognition in Mismatch-Repair Process Revealed

Accurate duplication of a cell's DNA is essential for the viability and controlled growth of that cell. But DNA replication occurs frequently and rapidly, so errors occur. The result is incorrect pairing of the 'bases' that make up the rungs of a DNA ladder. If these mistakes are not fixed, mutations can accumulate, so the error-correcting - 'mismatch-repair' - proteins are crucial. Errors can also occur in the genes encoding these proteins, resulting in high mutation rates and harmful effects. For example, inherited defects in some human mismatch-repair genes cause a common syndrome characterized by a predisposition to cancer, and errors in these genes in non-reproductive cells underlie some sporadic cancers.

The essential proteins in the mismatch-repair process are those that actually recognize mispairs. The structural basis of this recognition process for two bacterial proteins thought to act in a very similar manner to their closely related mammalian counterparts is revealed in two articles this week (Nature, Vol. 407, No. 6805, 12 Oct 2000). This research, from Titia K. Sixma of the Netherlands Cancer Institute, Amsterdam, The Netherlands, and colleagues, and Wei Yang and colleagues of the National Institutes of Health, Bethesda, Maryland, may ultimately lead to the rational design of cancer therapy strategies influencing this DNA repair pathway.

"This [research] is a wonderful example of how basic science and clinical care can help each other," comments Richard D. Kolodner of the San Diego School of Medicine, La Jolla, California, in an accompanying News and Views article.

CONTACT:

Titia K. Sixma
tel +31 20 5121 959
fax +31 20 512 1954
e-mail sixma@nki.nl

Wei Yang
tel +1 301 402 4645
fax +1 301 496 0201
e-mail Wei.Yang@nih.gov

Richard D. Kolodner
tel +1 619 534 7804
fax +1 858 534 7750
e-mail rkolodner@ucsd.edu

(C) Nature press release.

Message posted by: Trevor M. D'Souza