Energetically equivalent structural transitions in the Rad17-Rad9-Hus1-Rad1-Rhino complex underlie the sequential progression from activation through maintenance to inactivation of the ATR-dependent DNA damage response.

ABSTRACT: Activation of the ATR-dependent DNA damage response (ATR-DDR) is well characterized; however, the molecular mechanisms underlying its maintenance and inactivation remain largely elusive. Rhino is the least understood component of ATR-DDR. Structural modeling and binding free energy calculations revealed structural remodeling involving Rad17, Rad9-Hus1-Rad1 (9-1-1), and Rhino during ATR-DDR progression. Biochemical and computational analyses revealed the competitive binding of Rad17 and Rhino to the 9-1-1 complex, suggesting a structural transition from the Rad17-9-1-1 complex to the Rhino-9-1-1 complex. The presence of two conserved KYxxL+ motifs in Rhino suggests that it bridges the two 9-1-1 complexes. This enables the polymerization of multiple 9-1-1 complexes through Rhino and explains

SUBMITTER: Fukumoto Y 

PROVIDER: S-EPMC12907562 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature