6exu
Crystal structure of the DNA binding domain of fission yeast Sap1Crystal structure of the DNA binding domain of fission yeast Sap1
Structural highlights
Function[SAP1_SCHPO] Binds to sequences required for mating-type switching. Makes a simultaneous contact with both the alpha and beta domains of the switch-activating site SAS1. Also binds to replication fork barrier 1 (RFB1) located within a 78 base pair sequence near the 3' end of the rRNA coding region. This leads to replication fork blockage. It binds the consensus sequence 5'-TA[AG]GCAGNTN[CT]AACG[AC]G-3'. Has a role in chromosome organization and integrity where it is involved in chromosome segregation. Has a role in sister chromatid cohesion and condensation. Publication Abstract from PubMedThe 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. Structure of the replication regulator Sap1 reveals functionally important interfaces.,Jorgensen MM, Ekundayo B, Zaratiegui M, Skriver K, Thon G, Schalch T Sci Rep. 2018 Jul 19;8(1):10930. doi: 10.1038/s41598-018-29198-9. PMID:30026545[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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