Evolution of DNA replication origin specification and gene silencing mechanisms.

Hu, Y, Tareen, A., Sheu, Y. J., Ireland, W. T., Speck, C., Li, H., Joshua-Tor, L., Kinney, J. B., Stillman, B. (October 2020) Evolution of DNA replication origin specification and gene silencing mechanisms. Nature Communications, 11 (1). p. 5175. ISSN 2041-1723

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URL: https://pubmed.ncbi.nlm.nih.gov/33056978/
DOI: 10.1038/s41467-020-18964-x

Abstract

DNA replication in eukaryotic cells initiates from replication origins that bind the Origin Recognition Complex (ORC). Origin establishment requires well-defined DNA sequence motifs in Saccharomyces cerevisiae and some other budding yeasts, but most eukaryotes lack sequence-specific origins. A 3.9 Å structure of S. cerevisiae ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) bound to origin DNA revealed that a loop within Orc2 inserts into a DNA minor groove and an α-helix within Orc4 inserts into a DNA major groove. Using a massively parallel origin selection assay coupled with a custom mutual-information-based modeling approach, and a separate analysis of whole-genome replication profiling, here we show that the Orc4 α-helix contributes to the DNA sequence-specificity of origins in S. cerevisiae and Orc4 α-helix mutations change genome-wide origin firing patterns. The DNA sequence specificity of replication origins, mediated by the Orc4 α-helix, has co-evolved with the gain of ORC-Sir4-mediated gene silencing and the loss of RNA interference.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > origin recognition complex
organism description > yeast
CSHL Authors:
Communities: CSHL labs > Joshua-Tor lab
CSHL labs > Kinney lab
CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: Matthew Dunn
Date: 14 October 2020
Date Deposited: 03 Dec 2020 19:21
Last Modified: 23 Apr 2021 15:18
PMCID: PMC7560902
Related URLs:
URI: https://repository.cshl.edu/id/eprint/39832

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