Context based computational analysis and characterization of ARS consensus sequences (ACS) of Saccharomyces cerevisiae genome

Genome-wide experimental studies in Saccharomyces cerevisiae reveal that autonomous replicating sequence (ARS) requires an essential consensus sequence (ACS) for replication activity. Computational studies identified thousands of ACS like patterns in the genome. However, only a few hundreds of these...

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Main Authors: Singh, Vinod Kumar, Krishnamachari, Annangarachari
Format: Online
Language:English
Published: Elsevier 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971157/
id pubmed-4971157
recordtype oai_dc
spelling pubmed-49711572016-08-09 Context based computational analysis and characterization of ARS consensus sequences (ACS) of Saccharomyces cerevisiae genome Singh, Vinod Kumar Krishnamachari, Annangarachari Regular Article Genome-wide experimental studies in Saccharomyces cerevisiae reveal that autonomous replicating sequence (ARS) requires an essential consensus sequence (ACS) for replication activity. Computational studies identified thousands of ACS like patterns in the genome. However, only a few hundreds of these sites act as replicating sites and the rest are considered as dormant or evolving sites. In a bid to understand the sequence makeup of replication sites, a content and context-based analysis was performed on a set of replicating ACS sequences that binds to origin-recognition complex (ORC) denoted as ORC-ACS and non-replicating ACS sequences (nrACS), that are not bound by ORC. In this study, DNA properties such as base composition, correlation, sequence dependent thermodynamic and DNA structural profiles, and their positions have been considered for characterizing ORC-ACS and nrACS. Analysis reveals that ORC-ACS depict marked differences in nucleotide composition and context features in its vicinity compared to nrACS. Interestingly, an A-rich motif was also discovered in ORC-ACS sequences within its nucleosome-free region. Profound changes in the conformational features, such as DNA helical twist, inclination angle and stacking energy between ORC-ACS and nrACS were observed. Distribution of ACS motifs in the non-coding segments points to the locations of ORC-ACS which are found far away from the adjacent gene start position compared to nrACS thereby enabling an accessible environment for ORC-proteins. Our attempt is novel in considering the contextual view of ACS and its flanking region along with nucleosome positioning in the S. cerevisiae genome and may be useful for any computational prediction scheme. Elsevier 2016-07-19 /pmc/articles/PMC4971157/ /pubmed/27508123 http://dx.doi.org/10.1016/j.gdata.2016.07.005 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Singh, Vinod Kumar
Krishnamachari, Annangarachari
spellingShingle Singh, Vinod Kumar
Krishnamachari, Annangarachari
Context based computational analysis and characterization of ARS consensus sequences (ACS) of Saccharomyces cerevisiae genome
author_facet Singh, Vinod Kumar
Krishnamachari, Annangarachari
author_sort Singh, Vinod Kumar
title Context based computational analysis and characterization of ARS consensus sequences (ACS) of Saccharomyces cerevisiae genome
title_short Context based computational analysis and characterization of ARS consensus sequences (ACS) of Saccharomyces cerevisiae genome
title_full Context based computational analysis and characterization of ARS consensus sequences (ACS) of Saccharomyces cerevisiae genome
title_fullStr Context based computational analysis and characterization of ARS consensus sequences (ACS) of Saccharomyces cerevisiae genome
title_full_unstemmed Context based computational analysis and characterization of ARS consensus sequences (ACS) of Saccharomyces cerevisiae genome
title_sort context based computational analysis and characterization of ars consensus sequences (acs) of saccharomyces cerevisiae genome
description Genome-wide experimental studies in Saccharomyces cerevisiae reveal that autonomous replicating sequence (ARS) requires an essential consensus sequence (ACS) for replication activity. Computational studies identified thousands of ACS like patterns in the genome. However, only a few hundreds of these sites act as replicating sites and the rest are considered as dormant or evolving sites. In a bid to understand the sequence makeup of replication sites, a content and context-based analysis was performed on a set of replicating ACS sequences that binds to origin-recognition complex (ORC) denoted as ORC-ACS and non-replicating ACS sequences (nrACS), that are not bound by ORC. In this study, DNA properties such as base composition, correlation, sequence dependent thermodynamic and DNA structural profiles, and their positions have been considered for characterizing ORC-ACS and nrACS. Analysis reveals that ORC-ACS depict marked differences in nucleotide composition and context features in its vicinity compared to nrACS. Interestingly, an A-rich motif was also discovered in ORC-ACS sequences within its nucleosome-free region. Profound changes in the conformational features, such as DNA helical twist, inclination angle and stacking energy between ORC-ACS and nrACS were observed. Distribution of ACS motifs in the non-coding segments points to the locations of ORC-ACS which are found far away from the adjacent gene start position compared to nrACS thereby enabling an accessible environment for ORC-proteins. Our attempt is novel in considering the contextual view of ACS and its flanking region along with nucleosome positioning in the S. cerevisiae genome and may be useful for any computational prediction scheme.
publisher Elsevier
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971157/
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