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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