Excision of beta-L- and beta-D-nucleotide analogs from DNA by p53 protein.
The tumor suppressor p53 protein plays a critical role in the cell-cycle progression. The role of the 3'-to-5' exonuclease activity of p53 protein in the DNA repair process remains elusive. Using an in vitro exonuclease assay and defined oligonucleotides terminated with beta-D- and beta-L-nucleoside analogs at the 3'-terminus, we studied the ability of p53 protein to excise beta-L- and beta-D-nucleoside analogs which have anticancer or antiviral potential. p53 protein removes beta-D-nucleoside analogs more efficiently compared to that of beta-L-nucleoside analogs. The affinity of p53 protein for an beta-L-nucleotide terminated primer was 5 fold lower compared to non-modified primer. The hypothesis on an important role of the 3'-to-5' exonuclease activity of p53 protein in the action of nucleoside analogs was proposed.
Kukhanova
M
M
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Liu
T W
TW
Pelicano
H
H
Cheng
Y C
YC
D000970:Antineoplastic Agents / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D005092:Exonucleases / Q000737:chemistry*; D006801:Humans; D009705:Nucleosides / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009705:Nucleosides; D016159:Tumor Suppressor Protein p53; D004247:DNA; D005092:Exonucleases