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Interactions between p53, hMSH2-hMSH6 and HMG I(Y) on Holliday junctions and bulged bases

Deepa Subramanian1, Jack D Griffith

  • 1Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, CB 7295 Mason Farm Road, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.

Nucleic Acids Research
|May 30, 2002
PubMed

Insights

The tumor suppressor protein p53

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The tumor suppressor protein p53 plays a critical role in cellular response to DNA damage.
  • p53's DNA binding is modulated by post-translational modifications and protein interactions.
  • Understanding these interactions is key to deciphering p53's function in DNA repair.

Purpose of the Study:

  • To investigate the impact of nuclear proteins HMG-1, HMG I(Y), and hMSH2-hMSH6 on p53's DNA lesion binding.
  • To elucidate how these proteins modulate p53's interaction with damaged DNA substrates.

Main Methods:

  • Utilized gel retardation assays to study protein-DNA interactions.
  • Employed substrates mimicking DNA lesions, specifically Holliday junctions and extra base bulges.
  • Assessed the effects of HMG-1, HMG I(Y), and hMSH2-hMSH6 on p53 binding.

Main Results:

  • HMG-1 showed no significant effect on p53 binding to either substrate.
  • HMG I(Y) destabilized p53-Holliday junction complexes but not p53-bulge complexes.
  • The hMSH2-hMSH6 complex significantly enhanced p53 binding to both DNA substrates (3-4 fold).

Conclusions:

  • p53 DNA binding activity is dynamically regulated by interactions with other nuclear proteins.
  • Specific proteins can either inhibit (HMG I(Y)) or enhance (hMSH2-hMSH6) p53's DNA binding capabilities.
  • These findings highlight the complex regulatory network influencing p53's role in DNA damage response.

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