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Title: Structure of the replication regulator Sap1 reveals functionally important interfaces.
Authors: Jørgensen, MM
Ekundayo, B
Zaratiegui, M
Skriver, K
Thon, G
Schalch, T
First Published: 19-Jul-2018
Publisher: Nature Research (part of Springer Nature)
Citation: Scientific Reports, 2018, 8:10930
Abstract: The mechanism by which specific protein-DNA complexes induce programmed replication fork stalling in the eukaryotic genome remains poorly understood. In order to shed light on this process we carried out structural investigations on the essential fission yeast protein Sap1. Sap1 was identified as a protein involved in mating-type switching in Schizosaccharomyces pombe, and has been shown to be involved in programmed replication fork stalling. Interestingly, Sap1 assumes two different DNA binding modes. At the mating-type locus dimers of Sap1 bind the SAS1 sequence in a head-to-head arrangement, while they bind to replication fork blocking sites at rDNA and Tf2 transposons in a head-to-tail mode. In this study, we have solved the crystal structure of the Sap1 DNA binding domain and we observe that Sap1 molecules interact in the crystal using a head-to-tail arrangement that is compatible with DNA binding. We find that Sap1 mutations which alleviate replication-fork blockage at Tf2 transposons in CENP-B mutants map to the head-to-tail interface. Furthermore, several other mutations introduced in this interface are found to be lethal. Our data suggests that essential functions of Sap1 depend on its head-to-tail oligomerization.
DOI Link: 10.1038/s41598-018-29198-9
eISSN: 2045-2322
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: Coordinates and structure factors have been deposited in the Protein Data Bank under accession codes 6EXU (arsenic) and 6EXT (native). Supplementary information accompanies this paper at
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology

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