The disordered DNA-binding domain of p53 is indispensable for forming an encounter complex to and jumping along DNA

Dwiky Rendra Graha Subekti, Kiyoto Kamagata

Research output: Contribution to journalArticlepeer-review

Abstract

The tumor suppressor p53 utilizes a facilitated diffusion mechanism to search for and bind to target DNA sequences. Sub-millisecond single-molecule fluorescence tracking demonstrated that p53 forms a short-lived encounter complex to DNA then converts to the long-lived complex that can move and jump along DNA during the target search. To reveal the role of each DNA-binding domain of p53 in these processes, we investigated two p53 mutants lacking either of two DNA-binding domains; structured core and disordered C-terminal domains, using sub-millisecond single-molecule fluorescence microscopy. We found that the C-terminal domain is required for the encounter complex formation and conversion to the long-lived complex. The long-lived complex is stabilized by the core domain as well as the C-terminal domain. Furthermore, only the C-terminal domain participates in the jump of p53 along DNA at a high salt concentration. We propose that the flexible C-terminal domain of p53 is twined around DNA, which can form the encounter complex, convert to the long-lived complex, and enable p53 to land on DNA after the jump.

Original languageEnglish
Pages (from-to)21-26
Number of pages6
JournalBiochemical and biophysical research communications
Volume534
DOIs
Publication statusPublished - 2021 Jan 1

Keywords

  • DNA
  • Disordered
  • Jump
  • Single molecule
  • Transient complex
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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