Special Issue "DNA Replication"

Guest Editor
Prof. Dr. Peter Frank
Department of Medicine I / Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Wien, Austria
Website: http://www.meduniwien.ac.at/typo3/?id=4909
E-Mail: peter.frank@meduniwien.ac.at
Phone: +43 1 40160 57529
Fax: +43 1 40160 957500
Interests: enzymology of DNA replication and repair; RNA metabolism; molecular evolution of nucleases

Dear Colleagues,

Replication of DNA, even of the simplest one, is a very sophisticated process, depending on a complex enzymatic machinery being evolved over more than a billion of years. The proper action of replication is a prerequisite to maintain the genome integrity of all living organisms and together with other mechanisms it enables the evolution of life. On the one hand the universality of basic principles of duplication, derived from data obtained from the prokaryote kingdom of life, is an undisputed fact in our times. On the other hand the coordination of replication of eukaryotic genomes and the interaction between duplication and the cell division cycle is still a matter of intense research and debate. This special issue intends to demonstrate new developments and concepts in the general field of DNA replication and related topics, e.g. DNA repair. Research or review articles on any topic within the field will be considered. We are looking forward to your contributions.

Prof. Dr. Peter Frank 
Guest Editor

Submission

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• eukaryotic DNA replication
• replication fork dynamics
• origin
• priming
• Okazaki fragments
• DNA polymerases
• nucleases
• topoisomerases
• helicases

Type of Paper: Review
Title: Cellular Responses to Replication Stress: Implications in Cancer Biology and Therapy
Authors: Hui-Ju Hsieh and Guang Peng
Affiliation: Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Unit 1013, 6767 Bertner Avenue, Houston, Texas, 77030, USA; E-Mail: gpeng@mdanderson.org
Abstract: Replication stress is a characteristic feature of cancer cells, which is often resulted from excessive growth signaling induced by activation of oncogenes or loss of tumor suppressors. In precancerous and cancerous cells, replication stress primarily manifests as a high level of DNA double-strand breaks (DSBs) due to stalling and collapse of DNA replication forks. A key question remains unanswered: how do these cells survive with extensive DSBs caused by replication stress. In this review, we discuss cellular responses to replication stress including replication stress signaling, cell cycle checkpoint regulation, repair of replication lesions and the implications of these replication stress responses in cancer biology and therapy.

Type of Paper: Article
Title: Novel Functions for the Conserved Glutamate Residue in the Walker B Motif of Replication Factor C
Authors: Ankita Chiraniya¹, Jeff Finkelstein², Mike O'Donnell² and Linda B. Bloom¹
Affiliations: ¹ Department of Biochemistry & Molecular Biology, University of Florida, Gainesville, Fl 32605, USA; E-Mail: lbloom@ufl.edu
² Howard Hughes Medical Institute and the Rockefeller University, New York, NY 10021, USA
Abstract: Clamp loaders that load sliding clamps for DNA replication and repair are members of the AAA+ superfamily of ATPases. Conserved Walker B sequence elements in this family of ATPases contribute to ATP hydrolysis. Mutation of the Walker B glutamate in each of the four active sites of RFC reduces DNA-dependent ATP hydrolysis activity as expected, but unexpectedly reduce ATP-binding-dependent interactions with the clamp and DNA. A role for the Walker B glutamate in ATP-induced conformational changes in the clamp loader that promote ligand binding is a previously unknown function for this conserved Glu residue.

Type of Paper: Review
Title: The replication fork: understanding the eukaryotic DNA replication machinery and the challenges to genome duplication
Authors: Adam R. Leman and Eishi Noguchi *
Affiliation: Drexel University College of Medicine, Philadelphia, PA 19102, USA; E-Mail: eishi.noguchi@drexelmed.edu
Abstract: Eukaryotic cells must accurately and efficiently duplicate their genomes during each round of the cell cycle. Multiple linear chromosomes, an abundance of regulatory elements, and chromosome packaging are all challenges that eukaryotic DNA replication machinery must successfully overcome. The DNA replication machinery, the “replisome” complex, is composed of many specialized proteins with functions in supporting replication by DNA polymerases. Efficient replisome progression relies on tight coordination between the various factors of the replisome. Further, DNA replication progression must occur even on less than ideal templates at various genomic loci. Here, we describe the functions of the major replisome components, as well as some of the obstacles to efficient DNA replication that they confront. Together, this review summarizes current understanding of the vastly complicated task of replicating eukaryotic DNA.

Type of Paper: Review
Title: Molecular Mechanisms of DNA Replication Checkpoint Cctivation
Authors: Bénedicte Recolin, Siem Van der Laan and Domenico Maiorano
Affiliation: Genome Surveillance and Stability Laboratory, Institute of Human Genetics (IGH), CNRS - UPR 1142, 141 rue de la Cardonille, 34396 MONTPELLIER Cedex 5, France; E-Mail: Domenico.Maiorano@igh.cnrs.fr
Abstract: DNA synthesis is coupled to cell cycle progression. Progression of the replication fork during S-phase is monitored by a feedback mechanism known as S-phase checkpoint. This signalling pathway ensures that DNA synthesis has been completed once and only once in S-phase, before entering cell division. Failure to activate this checkpoint in response to inhibition of DNA synthesis (under replication) or to abnormal replication (over replication), results in chromosome fragmentation, aneuploidy and genomic instability. In this review we will describe the molecular determinants of the S-phase checkpoint in eukaryotic cells and discuss current model of activation of this signalling pathway.