A novel GT-mismatch binding protein that recognizes strict DNA sequences with high affinity.
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'-TRT GNB-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.
Takata-Yahiro
Maki
M
Department of Host-Defense Biochemistry, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
Fujii
Yoshito
Y
Nodarse
Jorge Fraga
JF
Islam
Mohammed Rafiqul
MR
Oda
Shinya
S
Zhang
Qiu-Mei
QM
Yonei
Shuji
S
Nakamura
Michio
M
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D020137:Base Pair Mismatch; D001483:Base Sequence; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D051719:MutS DNA Mismatch-Binding Protein; D009690:Nucleic Acid Conformation; D010084:Oxidation-Reduction; D013936:Thymidine / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D006147:Guanine; D000251:Adenosine Triphosphatases; D051719:MutS DNA Mismatch-Binding Protein; D013936:Thymidine