Mechanisms of loading and release of the 9-1-1 checkpoint clamp Journal Article


Authors: Castaneda, J. C.; Schrecker, M.; Remus, D.; Hite, R. K.
Article Title: Mechanisms of loading and release of the 9-1-1 checkpoint clamp
Abstract: Single-stranded or double-stranded DNA junctions with recessed 5′ ends serve as loading sites for the checkpoint clamp, 9-1-1, which mediates activation of the apical checkpoint kinase, ATRMec1. However, the basis for 9-1-1’s recruitment to 5′ junctions is unclear. Here, we present structures of the yeast checkpoint clamp loader, Rad24-replication factor C (RFC), in complex with 9-1-1 and a 5′ junction and in a post-ATP-hydrolysis state. Unexpectedly, 9-1-1 adopts both closed and planar open states in the presence of Rad24-RFC and DNA. Moreover, Rad24-RFC associates with the DNA junction in the opposite orientation of processivity clamp loaders with Rad24 exclusively coordinating the double-stranded region. ATP hydrolysis stimulates conformational changes in Rad24-RFC, leading to disengagement of DNA-loaded 9-1-1. Together, these structures explain 9-1-1’s recruitment to 5′ junctions and reveal new principles of sliding clamp loading. © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
Journal Title: Nature Structural and Molecular Biology
Volume: 29
Issue: 4
ISSN: 1545-9993
Publisher: Nature Publishing Group  
Date Published: 2022-04-01
Start Page: 369
End Page: 375
Language: English
DOI: 10.1038/s41594-022-00741-7
PUBMED: 35314831
PROVIDER: scopus
PMCID: PMC9027968
DOI/URL:
Notes: Article -- Export Date: 25 April 2022 -- Source: Scopus
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MSK Authors
  1. Dirk Remus
    14 Remus
  2. Richard Kevin Hite
    12 Hite