TY - JOUR
T1 - Function of the loop residue Thr792 in human DNA topoisomerase IIα
AU - Suda, Namiko
AU - Nakagawa, Yoshiyuki
AU - Kikuchi, Akihiko
AU - Sawada, Masako
AU - Takami, Yuko
AU - Funahashi, Hiro Omi
AU - Nakao, Akimasa
AU - Yoshida, Shonen
AU - Suzuki, Motoshi
N1 - Funding Information:
We thank Ms. Tazuko Tomita for sequencing support, Tatsuhiro Hirano for technical assistance, and Yasutomo Ito for constructing a model structure. This work was supported by Aichi Cancer Research Foundations.
PY - 2003/3/28
Y1 - 2003/3/28
N2 - We studied the mutation effect of one of the putative loop residues Thr792 in human DNA topoisomerase IIα (TOP2α). Thr792 mutants were expressed from high or low copy plasmids in a temperature sensitive yeast strain deficient in TOP2 (top2-1). When expressed from a high copy plasmid, mutants with small side chains complemented the yeast defect; however, from a low copy plasmid, only wild-type, Ser, and Cys substitution mutants complemented the yeast defect. Interestingly, at the permissive temperature other mutants (e.g., Val, Gly, and Glu substitutions) showed the dominant negative effect to the top2-1 allele, which was not observed by the control α4-helix mutants. T792E mutant was 10-fold less active than wild-type and the T792P had no decatenation activity in vitro. These results suggest that Thr792 in human TOP2α is involved in enzyme catalysis.
AB - We studied the mutation effect of one of the putative loop residues Thr792 in human DNA topoisomerase IIα (TOP2α). Thr792 mutants were expressed from high or low copy plasmids in a temperature sensitive yeast strain deficient in TOP2 (top2-1). When expressed from a high copy plasmid, mutants with small side chains complemented the yeast defect; however, from a low copy plasmid, only wild-type, Ser, and Cys substitution mutants complemented the yeast defect. Interestingly, at the permissive temperature other mutants (e.g., Val, Gly, and Glu substitutions) showed the dominant negative effect to the top2-1 allele, which was not observed by the control α4-helix mutants. T792E mutant was 10-fold less active than wild-type and the T792P had no decatenation activity in vitro. These results suggest that Thr792 in human TOP2α is involved in enzyme catalysis.
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U2 - 10.1016/S0006-291X(03)00297-3
DO - 10.1016/S0006-291X(03)00297-3
M3 - Article
C2 - 12646164
AN - SCOPUS:0242286178
VL - 303
SP - 46
EP - 51
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -