Humanizing the yeast origin recognition complex.

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Abstrakt

Tytuł:: Humanizing the yeast origin recognition complex.
Autorzy:: Lee CSK; School of Biological Sciences, The University of Hong Kong, Pok Fu Lam Road, Hong Kong.
Cheung MF; Center for Epigenomics Research, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong.; Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong.
Li J; Quantitative and Computational Biology, Departments of Biological Sciences, Chemistry, Physics & Astronomy, and Computer Science, University of Southern California, Los Angeles, CA, 90089, USA.
Zhao Y; Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong.; Institute for Advanced Study, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong.
Lam WH; School of Biological Sciences, The University of Hong Kong, Pok Fu Lam Road, Hong Kong.
Ho V; Center for Epigenomics Research, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong.; Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong.
Rohs R; Quantitative and Computational Biology, Departments of Biological Sciences, Chemistry, Physics & Astronomy, and Computer Science, University of Southern California, Los Angeles, CA, 90089, USA.
Zhai Y; School of Biological Sciences, The University of Hong Kong, Pok Fu Lam Road, Hong Kong. .
Leung D; Center for Epigenomics Research, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong. .; Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong. .
Tye BK; Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong. .; Institute for Advanced Study, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong. .; Department of Molecular Biology & Genetics, Cornell University, Ithaca, NY, 14853, USA. .
Źródło:: Nature communications [Nat Commun] 2021 Jan 04; Vol. 12 (1), pp. 33. Date of Electronic Publication: 2021 Jan 04.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : Nature Pub. Group
MeSH Terms:: Origin Recognition Complex/*metabolism
Saccharomyces cerevisiae/*metabolism
Amino Acid Sequence ; Base Sequence ; Binding Sites ; DNA, Fungal/metabolism ; G2 Phase/genetics ; Genome, Fungal ; Humans ; Models, Genetic ; Mutation/genetics ; Nucleosomes/metabolism ; Nucleotide Motifs/genetics ; Origin Recognition Complex/chemistry ; S Phase ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Stochastic Processes ; Transcription Initiation Site
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Grant Information:: R35 GM130376 United States GM NIGMS NIH HHS
Substance Nomenclature:: 0 (DNA, Fungal)
0 (Nucleosomes)
0 (Origin Recognition Complex)
0 (Saccharomyces cerevisiae Proteins)
Entry Date(s):: Date Created: 20210105 Date Completed: 20210113 Latest Revision: 20210407
Update Code:: 20240105
PubMed Central ID:: PMC7782691
DOI:: 10.1038/s41467-020-20277-y
PMID:: 33397927
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The Origin Recognition Complex (ORC) is an evolutionarily conserved six-subunit protein complex that binds specific sites at many locations to coordinately replicate the entire eukaryote genome. Though highly conserved in structure, ORC's selectivity for replication origins has diverged tremendously between yeasts and humans to adapt to vastly different life cycles. In this work, we demonstrate that the selectivity determinant of ORC for DNA binding lies in a 19-amino acid insertion helix in the Orc4 subunit, which is present in yeast but absent in human. Removal of this motif from Orc4 transforms the yeast ORC, which selects origins based on base-specific binding at defined locations, into one whose selectivity is dictated by chromatin landscape and afforded with plasticity, as reported for human. Notably, the altered yeast ORC has acquired an affinity for regions near transcriptional start sites (TSSs), which the human ORC also favors.

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