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J. Biol. Chem., Vol. 276, Issue 21, 17727-17731, May 25, 2001
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From the Departments of Despite the importance of the topoisomerase II
DNA cleavage/rejoining cycle to genomic integrity, the mechanistic
details of religation are poorly understood. Topoisomerase II
utilizes covalent protein-DNA interactions to align the 5'-termini of
cleaved DNA for religation. However, because the enzyme does not form covalent bonds with the 3'-DNA termini, the basis for the alignment of
the 3'-ends is less clear. Three major possibilities exist. The
3'-termini may be positioned for religation (i) by base pairing to
their complementary DNA strands, (ii) by base stacking to the adjacent
residues, or (iii) by noncovalent interactions with topoisomerase II.
To distinguish between these possibilities, the ability of human
topoisomerase II
Positioning the 3'-DNA Terminus for Topoisomerase II-mediated
Religation*
§ and¶
Biochemistry and
¶ Medicine (Hematology/Oncology), Vanderbilt University School of
Medicine, Nashville, Tennessee 37232-0146
to religate a series of oligonucleotides with
altered base pairing or base stacking at their 3'-termini was
determined. Substrates containing modifications that disrupted terminal
base pairing or base stacking with-out affecting the 3'-terminal base
were resealed at wild-type rates. In contrast, substrates that lacked
the terminal base (or contained an altered base) displayed very low
rates of religation. On the basis of these results, we propose
that topoisomerase II positions the 3'-DNA termini for religation
through noncovalent protein-DNA contacts.
*
This work was supported by Grants GM33944 and GM53960 from
the National Institutes of Health.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Biochemistry, 654 Robinson Research Bldg., Vanderbilt University School of Medicine, Nashville, TN 37232-0146. Tel.: 615-322-4338; Fax: 615-343-1166; E-mail: osheron@ctrvax.vanderbilt.edu.
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