The interaction of p53 with 3′-terminal mismatched DNA

Mary Bakhanashvili, Amnon Hizi, Galia Rahav

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


The diversity of p53 functions involves its interaction with sequence-specific, non-sequence-specific and various damaged sites in DNA. The preferential excision of misincorporated over correct nucleotides by the 3′→5′ exonuclease activity of p53 provides a molecular basis for p53 involvement in the correction of the DNA replication errors. However, p53 exhibits variations in its comparative efficiency to excise different 3′-terminal mismatched nucleotides. To determine the importance of the binding capacity of the protein to various 3′-terminal damaged sites, we have examined the interaction of p53 with linear dsDNAs containing various 3′-terminal mismatches by employing a gel retardation assay. The data demonstrate the intrinsic 3′-terminal mismatched DNA binding capacity of p53. Since p53 binds directly to various 3′-terminal purine:pyrimidine and purine:purine mispairs to an equal extent, it can be considered a general 3′-mismatched DNA binding protein. Apparently, 3′-terminal mismatched bases are structural elements to which p53 can bind, that extends the spectrum of damage sites to which p53 may respond. The formation of the p53-mismatched DNA complex is independent of the sequence context. Thus, the dissimilarities in mispair excision efficiency are probably due to an inherent property of the p53 in the excision of 3′-mismatched nucleotides by a bound protein. the results establish a framework for understanding the mechanism of cooperative interaction between p53 and exonuclease-deficient DNA polymerase (e.g., HIV-1 RT). Within the context of error-correction events, p53 by recognition and excision of 3′-mismatched nucleotides, may be involved in DNA repair, thus increasing the accuracy of DNA synthesis by DNA polymerases.

Original languageEnglish
Pages (from-to)1380-1389
Number of pages10
JournalCell Cycle
Issue number7
StatePublished - 1 Apr 2010


  • 3′-terminal mismatched DNA
  • DNA binding
  • Exonuclease
  • Mismatch excision
  • p53


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