Nucleic Acids Research Advance Access originally published online on December 9, 2008
Nucleic Acids Research 2009 37(2):568-581; doi:10.1093/nar/gkn974
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Nucleic Acids Research, 2009, Vol. 37, No. 2 568-581
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Physical and functional interactions between human mitochondrial single-stranded DNA-binding protein and tumour suppressor p53
1Centre for Protein Engineering and 2Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 0QH, UK
*To whom correspondence should be addressed. Tel: +44 1223 402137; Fax: +44 1223 402140; Email: arf25{at}cam.ac.uk
Received September 18, 2008. Revised November 13, 2008. Accepted November 19, 2008.
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) µM. 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.
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