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Molecular and Cellular Biology, September 1998, p. 5332-5342, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Specific Mismatch Recognition in Heteroduplex
Intermediates by p53 Suggests a Role in Fidelity Control of
Homologous Recombination
Christine
Dudenhöffer,
Gabor
Rohaly,
Katrin
Will,
Wolfgang
Deppert, and
Lisa
Wiesmüller*
Heinrich-Pette-Institut für
Experimentelle Virologie und Immunologie an der Universität
Hamburg, D-20251 Hamburg, Germany
Received 2 February 1998/Returned for modification 30 March
1998/Accepted 23 June 1998
We demonstrate that wild-type p53 inhibits homologous
recombination. To analyze DNA substrate specificities in this process, we designed recombination experiments such that coinfection of simian
virus 40 mutant pairs generated heteroduplexes with distinctly unpaired
regions. DNA exchanges producing single C-T and A-G mismatches were
inhibited four- to sixfold more effectively than DNA exchanges producing G-T and A-C single-base mispairings or unpaired regions of
three base pairs comprising G-T/A-C mismatches. p53 bound specifically to three-stranded DNA substrates, mimicking early recombination intermediates. The KD values for the
interactions of p53 with three-stranded substrates displaying
differently paired and unpaired regions reflected the mismatch base
specificities observed in recombination assays in a qualitative and
quantitative manner. On the basis of these results, we would like to
advance the hypothesis that p53, like classical mismatch repair
factors, checks the fidelity of homologous recombination processes by
specific mismatch recognition.
*
Corresponding author. Mailing address:
Heinrich-Pette-Institut, Martinistrasse 52, 20251 Hamburg, Germany.
Phone: 49-40-48051-234. Fax: 49-40-48051-117. E-mail:
wiesmuel{at}plexus.uke.uni-hamburg.de.
Molecular and Cellular Biology, September 1998, p. 5332-5342, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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