Dimitris Polychronopoulos

Publications (3) View all

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  Available from: Dimitris Polychronopoulos

  Conference Proceeding: Analyzing the DNA composition of ultraconserved sequences with N-gram Graphs

  D Polychronopoulos, G Giannakopoulos, C Nikolaou, G Paliouras, Y Almirantis
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  ABSTRACT: Motivation: One of the most striking discoveries to have emerged from comparisons among mammalian and other genomes is the existence of hundreds of noncoding elements of more than 200 bp in length that show absolute identity among mammalian orders [1]. These elements represent the tip of the iceberg of a much larger class of conserved noncoding elements (CNEs). There have been many speculations about what the exact role of these elements may be, proposing that they might act as enhancers [2] or even insulators [3]. The diverse nature of these elements appears to be in contrast with their very particular DNA composition, the study of which may provide us with insight on their possible functional roles. To date, base composition analysis has been confined to conventional methods of statistical over/under-representations. Herein, we attempt to assess the nucleotide usage preferences in greater detail with the use of a powerful machine learning approach. Methods: Ultraconserved sequences for H.sapiens and C. elegans were obtained and analyzed through the N-gram Graph approach [4]. The N-gram graphs (NGG) represent how symbols (e.g., nucleotides) co-occur within a given neighborhood (e.g., within an oligonucleotide). The neighborhood is defined based on a distance function (e.g., a neighborhood of 5 consecutive bases in a genomic sequence). Under this framework we trained graphs with the UCS and compared them with genomic and random surrogate sequences with similar DNA composition, in order to define specific "rules" in the use of nucleotides existing within UCS. Results: NGG-assisted classification of UCS and CNEs (sequences obtained with less stringent conservation criteria) against random genomic sequences with identical composition was accurate at a rate of 76%. CNEs were better distinguished from random sequences with identical composition than from natural genomic sequences with the same GC content. Furthermore, a classification of different collections of conserved non-coding sequences from H. sapiens and C. elegans revealed differences among
  HSCBB 2011 Conference, Patras, Greece; 10/2011
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  Available from: Dimitris Polychronopoulos

  Conference Proceeding: A study of the genomic distribution of Conserved Noncoding Elements in several organisms: Global genomic organization expressed in the form of power laws

  Polychronopoulos D, Sellis D, Almirantis Y
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  ABSTRACT: In continuation of recent works by our research group for other classes of genomic sequences (such as coding segments and repetitive elements, and given the possible implication of CNEs’ in gene regulation) we have studied the distribution of inter-CNE distances in a variety of sequenced genomes. In most cases these distributions have been found to be power-law-like.
  Hellenic Society for Computational Biology and Bioinformatics 2010 Conference, Alexandroupolis; 01/2010
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  Available from: Agnieszka Gambus

  Article: A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome.

  Agnieszka Gambus, Frederick van Deursen, Dimitrios Polychronopoulos, Magdalena Foltman, Richard C Jones, Ricky D Edmondson, Arturo Calzada, Karim Labib
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  ABSTRACT: The eukaryotic replisome is a crucial determinant of genome stability, but its structure is still poorly understood. We found previously that many regulatory proteins assemble around the MCM2-7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2-7 to other replisome components. Here, we show that the RPC associates with DNA polymerase alpha that primes each Okazaki fragment during lagging strand synthesis. Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha. Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks. We show that cells lacking both Ctf4 and Mrc1 experience chronic activation of the DNA damage checkpoint during chromosome replication and do not complete the cell cycle. These findings indicate that coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this process.
  The EMBO Journal 09/2009; 28(19):2992-3004. · 9.20 Impact Factor