A model for the mechanism of human topoisomerase I

Journal Article · Fri Mar 06 04:00:00 EST 1998 · Science

DOI:https://doi.org/10.1126/science.279.5356.1534· OSTI ID:621406

Stewart, L; Redinbo, M R; Qiu, X ^[1]

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1. Univ. of Washington, Seattle, WA (United States); and others

The three-dimensional structure of a 70-kilodalton amino terminally truncated form of human topoisomerase I in complex with a 22-base pair duplex oligonucleotide, determined to a resolution of 2.8 angstroms, reveals all of the structural elements of the enzyme that contact DNA. The linker region that connects the central core of the enzyme to the carboxyl-terminal domain assumes a coiled-coil configuration and protrudes away from the remainder of the enzyme. The positively charged DNA-proximal surface of the linker makes only a few contacts with the DNA downstream of the cleavage site. In combination with the crystal structures of the reconstituted human topoisomerase I before and after DNA cleavage, this information suggests which amino acid residues are involved in catalyzing phosphodiester bond breakage and religation. The structures also lead to the proposal that the topoisomerization step occurs by a mechanism termed controlled rotation. 30 refs., 4 figs., 1 tab.

• OSTI ID: 621406
• Journal Information: Science, Journal Name: Science Journal Issue: 5356 Vol. 279; ISSN SCIEAS; ISSN 0036-8075
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DNA REPLICATION
ENZYMES
ISOMERASES
MAN
TRANSCRIPTION