Physical and functional interactions between human mitochondrial single-stranded DNA-binding protein and tumour suppressor p53.

Single-stranded DNA-binding proteins (SSB) form a class of proteins that bind preferentially single-stranded DNA with high affinity. They are involved in DNA metabolism in all organisms and serve a vital role in replication, recombination and repair of DNA. In this report, we identify human mitochondrial SSB (HmtSSB) as a novel ...
protein-binding partner of tumour suppressor p53, in mitochondria. It binds to the transactivation domain (residues 1-61) of p53 via an extended binding interface, with dissociation constant of 12.7 (+/- 0.7) microM. Unlike most binding partners reported to date, HmtSSB interacts with both TAD1 (residues 1-40) and TAD2 (residues 41-61) subdomains of p53. HmtSSB enhances intrinsic 3'-5' exonuclease activity of p53, particularly in hydrolysing 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) present at 3'-end of DNA. Taken together, our data suggest that p53 is involved in DNA repair within mitochondria during oxidative stress. In addition, we characterize HmtSSB binding to ssDNA and p53 N-terminal domain using various biophysical measurements and we propose binding models for both.
Mesh Terms:
8-Hydroxy-2'-Deoxyguanosine, Binding Sites, Cell Line, Tumor, DNA Polymerase gamma, DNA, Single-Stranded, DNA-Binding Proteins, DNA-Directed DNA Polymerase, Deoxyguanosine, Exodeoxyribonucleases, Humans, Mitochondrial Proteins, Protein Binding, Protein Stability, Protein Structure, Tertiary, Temperature, Tumor Suppressor Protein p53
Nucleic Acids Res
Date: Feb. 01, 2009
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