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ABSTRACT p53 plays a central role in the maintenance of the genome integrity, both as a gatekeeper and a caretaker. Sequence-specific recognition of DNA is underlying the ability of p53 to

transcriptionally transactivate target genes during checkpoint control and to regulate DNA replication at the TGCCT repeat from the ribosomal gene cluster (RGC). In contrast, suppression of

recombination by p53 has been observed with nonconsensus DNA sequences. In this study, we discovered that wild-type p53 stimulates homologous recombination adjacent to the RGC repeat,

whereas downregulation is seen with a mutated version thereof and with a microsatellite repeat sequence. Analysis of the causes possibly underlying the enhancement of homologous

recombination revealed that p53 binding to the RGC element delays DNA synthesis. This was demonstrated after integration of the corresponding DNA fragments into our Simian virus 40-based

model system, which was used to study recombination on replicating minichromosomes. Differently, with plasmid-based substrates, p53 did not stimulate recombination at the RGC sequence. Thus,

in combination with our previous findings, p53 may promote homologous recombination by two separate mechanisms involving either molecular interactions with topoisomerase I or/and by

specific binding to certain genomic regions, thereby causing replication fork stalling and recombination. Access through your institution Buy or subscribe This is a preview of subscription

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RECOMBINATION INDUCED BY A REPLICATION FORK BARRIER Article Open access 10 January 2022 P53 ISOFORMS DIFFERENTIALLY IMPACT ON THE POLΙ DEPENDENT DNA DAMAGE TOLERANCE PATHWAY Article Open

access 13 October 2021 THE NUCLEAR PORE PRIMES RECOMBINATION-DEPENDENT DNA SYNTHESIS AT ARRESTED FORKS BY PROMOTING SUMO REMOVAL Article Open access 06 November 2020 REFERENCES * Achanta G,

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_Mol. Cell. Biol._, 20, 5930–5938. Download references ACKNOWLEDGEMENTS We are grateful to Richard P Bowater, University of East Anglia Norwich, and Robert D Wells, Texas Medical Center, for

construct pRW3246, to Professor Dr B Vogelstein, John Hopkins Oncology Center, Baltimore, for pSK-45-13-2-PyCAT and pSK-89-15-1-PyCAT. We thank Evelyn Bendrat for experimental assistance

with DNA cloning. This work was supported by the Dr Mildred Scheel Stiftung (Deutsche Krebshilfe) Grant 10-1907-Wi 2, by the Deutsche Forschungsgemeinschaft Grant Wi 1376/3-1, and by the

Land Baden-Württemberg, Forschungsschwerpunktprogramm: Fehlregulation von Apoptose als Grundlage für Krankheit. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Universitätsfrauenklinik,

Prittwitzstrasse 43, D-89075, Ulm, Germany Gisa S Boehden, Cindy Baumann, Simone Siehler & Lisa Wiesmüller * Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der

Universität Hamburg, Martinistrasse 52, D-20251, Hamburg, Germany Gisa S Boehden & Lisa Wiesmüller Authors * Gisa S Boehden View author publications You can also search for this author

inPubMed Google Scholar * Cindy Baumann View author publications You can also search for this author inPubMed Google Scholar * Simone Siehler View author publications You can also search for

this author inPubMed Google Scholar * Lisa Wiesmüller View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Lisa

Wiesmüller. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Boehden, G., Baumann, C., Siehler, S. _et al._ Wild-type p53 stimulates homologous

recombination upon sequence-specific binding to the ribosomal gene cluster repeat. _Oncogene_ 24, 4183–4192 (2005). https://doi.org/10.1038/sj.onc.1208592 Download citation * Received: 18

February 2004 * Revised: 01 February 2005 * Accepted: 04 February 2005 * Published: 14 March 2005 * Issue Date: 16 June 2005 * DOI: https://doi.org/10.1038/sj.onc.1208592 SHARE THIS ARTICLE

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by the Springer Nature SharedIt content-sharing initiative KEYWORDS * homologous recombination * microsatellite repeat * p53 recognition sequence * replication-associated recombination