In Vivo Assay of P53 Function in Homologous Recombination Between Simian Virus 40 Chromosomes

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1996 Feb 1

PMID 8551610

Citations 17

Authors

L Wiesmuller

J Cammenga

W W Deppert

Affiliations

Soon will be listed here.

Abstract

To investigate a possible role of p53 in DNA exchange mechanisms, we have developed a model system which allows us to quantify homologous recombination rates in eukaryotic cells. We generated two types of simian virus 40 (SV40) whose genomes were mutated in such a way that upon double infection of monkey cells, virus particles can be released only after interchromosomal exchange of genetic material. This test system allowed us to determine recombination rates in the order of 10(-4) to 10(-6) for chromatin-associated SV40 genomes. To study the role of p53-T-antigen (T-Ag) complexes in this process, we designed viral test genomes with an additional mutation leading to a single amino acid exchange in T-Ag (D402H) and specifically blocking T-Ag-p53 interactions. Analysis of primary rhesus monkey cells endogenously expressing wild-type p53 showed a decreased recombination rate upon loss of efficient T-Ag-p53 complex formation. However, cells expressing mutant p53 (LLC-MK2 cells), the introduction of mutant T-Ag did not affect the DNA exchange rates. Our data are interpreted to indicate an inhibitory role of wild-type p53 in recombination. In agreement with this hypothesis, p53-T-Ag complex formation alleviates the inhibitory effect of wild-type p53.

Citing Articles

Methods for Enhancing Clustered Regularly Interspaced Short Palindromic Repeats/Cas9-Mediated Homology-Directed Repair Efficiency.

Tang X, Gao F, Liu M, Fan Q, Chen D, Ma W Front Genet. 2019; 10:551.

PMID: 31263478 PMC: 6590329. DOI: 10.3389/fgene.2019.00551.

p53 null fluorescent yellow direct repeat (FYDR) mice have normal levels of homologous recombination.

Wiktor-Brown D, Sukup-Jackson M, Fakhraldeen S, Hendricks C, Engelward B DNA Repair (Amst). 2011; 10(12):1294-9.

PMID: 21993421 PMC: 3217108. DOI: 10.1016/j.dnarep.2011.09.009.

Diversity of escape variant mutations in Simian virus 40 large tumor antigen (SV40 Tag) epitopes selected by cytotoxic T lymphocyte (CTL) clones.

Mylin L, Schell T, Epler M, Kusuma C, Assis D, Matsko C Virology. 2007; 364(1):155-68.

PMID: 17368499 PMC: 3866617. DOI: 10.1016/j.virol.2007.02.007.

Poly(ADP-RIBOSE) polymerase-1 (Parp-1) antagonizes topoisomerase I-dependent recombination stimulation by P53.

Baumann C, Boehden G, Burkle A, Wiesmuller L Nucleic Acids Res. 2006; 34(3):1036-49.

PMID: 16473854 PMC: 1363779. DOI: 10.1093/nar/gkj509.

Discriminatory suppression of homologous recombination by p53.

Yun S, Lie-A-Cheong C, Porter A Nucleic Acids Res. 2004; 32(22):6479-89.

PMID: 15601996 PMC: 545454. DOI: 10.1093/nar/gkh986.

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