Tohoku J. Exp. Med., 2003, 200 (4)

A Novel GT-Mismatch Binding Protein That Recognizes
Strict DNA Sequences with High Affinity

MAKI TAKATA-YAHIRO, YOSHITO FUJII, JORGE FRAGA NODARSE, MOHAMMED RAFIQUL ISLAM,
SHINYA ODA,¹ QIU-MEI ZHANG,² SHUJI YONEI² and MICHIO NAKAMURA

Department of Host-Defense Biochemistry, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523,
¹Institute for Clinical Research, National Kyushu Cancer Center, Fukuoka 811-1395, and
²Laboratory of Radiation Biology, Graduate School of Science, Kyoto University, Kyoto 606-8502

Mismatched or damaged base pairs in DNA are mutagenic and both eukaryotes and prokaryotes have a series of repair systems that decrease a spontaneous mutation rate. All exocyclic amino groups of cytosine(C), adenine(A), and guanine(G) contribute to hydrogen bonds for base pairing. High temperature and oxidative stresses increase the deamination of these bases and methylated C. These deaminated sites would be initially recognized by components of DNA repair system. We discovered a novel G/thymine(T)-mismatch binding protein (nGTBP) that bound, with high affinity, to a minimal 14-mer DNA heteroduplex with a strict 5´-TRTGNB-3´ sequence (R for purine, N for any bases, and B for “not A,” namely for C, G, or T ). This italicized G position mismatched with T could be replaced by hypoxanthine, the deaminated A. The nGTBP, however, barely recognized DNA duplexes individually containing 8-oxo-G, thymine glycol, and 5-methylcytosine.

keywords —— GT-mismatch binding protein; DNA repair; deamination; gp91^phox promoter

© 2003 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2003, 200, 211-229

Address for reprints: Michio Nakamura, M.D., Ph.D., Department of Host-Defense Biochemistry, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

e-mail: nakamura@net.nagasaki-u.ac.jp