Intrinsically disordered domain of tumor suppressor p53 facilitates target search by ultrafast transfer between different DNA strands.

ABSTRACT: Intersegmental transfer (IST) is an important strategy in the target search used by sequence-specific DNA-binding proteins (DBPs), enabling DBPs to search for targets between multiple DNA strands without dissociation. We examined the IST of the tumor suppressor p53 using ensemble stopped-flow and single-molecule fluorescence measurements. The ensemble measurements demonstrated that p53 exhibits very fast IST, whose rate constant was ∼108 M-1 s-1. To determine the domains of p53 responsible for IST, two mutants with deletions of one of its two DNA binding domains were generated. The mutant lacking the disordered C-terminal (CT) domain (the CoreTet mutant) abolished IST, whereas the mutant lacking the structured core domain (the TetCT mutant) maintained IST, clearly demonstrating the importa

SUBMITTER: Itoh Y 

PROVIDER: S-EPMC6101536 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature