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Linda H. Malkas - One of the best experts on this subject based on the ideXlab platform.

  • eLS - DNA Replication: Mammalian
    eLS, 2009
    Co-Authors: Brandy M. Snider, Robert J. Hickey, Elizabeth A. Phipps, Shanna J. Smith, Brittney-shea Herbert, Linda H. Malkas
    Abstract:

    Deoxyribonucleic acid (DNA) Replication is an evolutionarily semi-conserved process that involves a mechanism to unwind the parent DNA strand, the synthesis of identical daughter strands, and steps to terminate the sequence. Owing to the massive amount of genetic information needed to be copied error-free, the Replication of DNA within the mammalian chromosome is highly complex, requiring the simultaneous firing of multiple origins and processing of DNA at defined sites within the cells. This action requires the strict regulation and precise timing of numerous proteins, enzymes and substrates. These components critical to DNA Replication will associate within these compartments in the cell to form Replication factories during processing. Although many of the basic functions of DNA synthesis are well-defined, there is still much yet to be understood regarding the machinery involved in the initiation, synthesis and termination of mammalian DNA Replication. Key Concepts: Mammalian DNA Replication occurs at specific regions within the cell. Proteins necessary for DNA Replication come together to form ‘Replication factories’ within the nucleus. The manner and timing of mammalian DNA Replication is largely determined in G1 of the cell cycle. The selection and timing of each Replication site is controlled by a combination of primary sequences, kinase activation, transcription, and local chromatin environment. The proteins thus far identified at the mammalian cell DNA Replication fork include the MCM helicase complex, DNA pol α-primase, PCNA, RFC, DNA pol δ, FEN1, RPA, DNA ligase I, topoisomerase I and II and RNAse H. Termination of mammalian DNA Replication is thought to be dependent on physical barriers within the Replication factories, as opposed to actual termination sequences within the DNA structure. In the event of Replication fork stalling, repair pathways must be activated to halt cell cycle progression and repair the damage. Keywords: DNA Replication; mammalian cells; Replication factories; initiation; Replication fork; termination; Replication fork stalling

  • DNA Replication machinery of the mammalian cell.
    Journal of Cellular Biochemistry, 1998
    Co-Authors: Linda H. Malkas
    Abstract:

    : The process of DNA Replication in mammalian cells is highly complex and has several unique features that distinguish it from simpler prokaryotic systems. The study of mammalian DNA Replication lagged behind that of prokaryotes for many years. This was because of the lack of a reliable and efficient mammalian cell-based in vitro DNA Replication system. In 1984, the first mammalian-based DNA Replication system that initiated DNA synthesis successfully in vitro was developed. The employment of the mammalian in vitro DNA Replication system has led to the identification of several DNA Replication proteins. This article describes the current knowledge regarding the proteins mediating mammalian DNA Replication, as well as how they are proposed to function during DNA synthesis. There is also a discussion of the role the mammalian cell nuclear architecture plays in DNA Replication. The evidence for the existence of an organized DNA Replication machine in mammalian cells is also presented.

  • Mammalian cell DNA Replication.
    Critical Reviews in Eukaryotic Gene Expression, 1997
    Co-Authors: Robert J. Hickey, Linda H. Malkas
    Abstract:

    : The precise mechanisms involved in the regulation of the mammalian cell DNA-synthesizing machinery are poorly understood. In vitro DNA Replication systems, in particular the employment of the simian virus 40 (SV40)-based cell-free DNA Replication system, has identified several mammalian enzymes and proteins required for DNA synthesis. Although these proteins have been identified as playing a role in DNA Replication, their functional organization allowing for the efficient Replication of DNA has not been well defined. This review describes the proteins that have currently been defined as having a role in mammalian DNA Replication and their proposed mechanisms of action. How these proteins may organize themselves to form multiprotein complexes, or larger DNA Replication factories, allowing for efficient chromosomal DNA synthesis is discussed. In addition, the cell cycle regulation of mammalian DNA synthesis and the current status concerning mammalian DNA Replication origins is described.

Margarita Salas - One of the best experts on this subject based on the ideXlab platform.

  • Compartmentalization of prokaryotic DNA Replication.
    Fems Microbiology Reviews, 2005
    Co-Authors: Alicia Bravo, Gemma Serrano-heras, Margarita Salas
    Abstract:

    It becomes now apparent that prokaryotic DNA Replication takes place at specific intracellular locations. Early studies indicated that chromosomal DNA Replication, as well as plasmid and viral DNA Replication, occurs in close association with the bacterial membrane. Moreover, over the last several years, it has been shown that some Replication proteins and specific DNA sequences are localized to particular subcellular regions in bacteria, supporting the existence of Replication compartments. Although the mechanisms underlying compartmentalization of prokaryotic DNA Replication are largely unknown, the docking of Replication factors to large organizing structures may be important for the assembly of active Replication complexes. In this article, we review the current state of this subject in two bacterial species, Escherichia coli and Bacillus subtilis, focusing our attention in both chromosomal and extrachromosomal DNA Replication. A comparison with eukaryotic systems is also presented.

  • Protein-priming of DNA Replication.
    Annual Review of Biochemistry, 1991
    Co-Authors: Margarita Salas
    Abstract:

    PERSPECTIVES AND SUMMARY . ....... . . . . . . . . . . . . ...... ... . . . . ... 40 ADENOVIRUS DNA Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . �;;,t���:��� �� �:�:o:::::::::::::::::::::: :::::::::::::::::::::::::::::::::::::::::::: :: :::::::::: Viral Proteins Required for Replication . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . Cell�lar Protei�s Required for Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Repitcatwn OT/gm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Replication of the Nontemplate Strand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACTERIOPHAGE 4>29 DNA Replication . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . .... ...... . . . . . Replication in Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Replication in Vitro . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . Viral Proteins Essential for the Initiation of Replication . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . Other Viral Proteins Involved in Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Repitcatwn OT/gm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Replication of the Nontemplate Strand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACTERIOPHAGE PRDI DNA Replication ....... . . . . . ....... . . . . . . . .. . . . . . . . ... . .... . . . BACTERIOPHAGE Cp-l DNA Replication . . . . . . . . . . . ...... ..... . . . ...... . . ... . BACTERIOPHAGE HB-3 TP .. . . . . . . . . . . . . . . . . . . . . ........ . . . . . . . . . . . . ....... .. . TERMINAL PROTEINS IN LINEAR PLASMIDS . . . . . . . . . . .... . .. . . . . . . . . . .... . . . . HEPADNAVIRUS TP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GENOME-LINKED PROTEINS OF RNA VIRUSES . . ....... . CONCLUSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Bruce Stillman - One of the best experts on this subject based on the ideXlab platform.

  • the DNA Replication fork in eukaryotic cells
    Annual Review of Biochemistry, 1998
    Co-Authors: Shou Waga, Bruce Stillman
    Abstract:

    Replication of the two template strands at eukaryotic cell DNA Replication forks is a highly coordinated process that ensures accurate and efficient genome duplication. Biochemical studies, principally of plasmid DNAs containing the Simian Virus 40 origin of DNA Replication, and yeast genetic studies have uncovered the fundamental mechanisms of Replication fork progression. At least two different DNA polymerases, a single-stranded DNA-binding protein, a clamp-loading complex, and a polymerase clamp combine to replicate DNA. Okazaki fragment synthesis involves a DNA polymerase-switching mechanism, and maturation occurs by the recruitment of specific nucleases, a helicase, and a ligase. The process of DNA Replication is also coupled to cell-cycle progression and to DNA repair to maintain genome integrity.

Stephen J Elledge - One of the best experts on this subject based on the ideXlab platform.

  • checking on the fork the DNA Replication stress response pathway
    Trends in Cell Biology, 2002
    Co-Authors: Alexander J Osborn, Stephen J Elledge
    Abstract:

    To ensure the fidelity of DNA Replication, cells activate a stress-response pathway when DNA Replication is perturbed. This pathway regulates not only progress through the cell cycle but also transcription, apoptosis, DNA repair/recombination and DNA Replication itself. Mounting evidence has suggested that this pathway is important for the maintenance of genomic integrity. Here, we discuss recent findings about how this pathway is activated by Replication stress and how it regulates the DNA-Replication machinery to alleviate the stress.

Anindya Dutta - One of the best experts on this subject based on the ideXlab platform.

  • initiation of DNA Replication in eukaryotic cells
    Annual Review of Cell and Developmental Biology, 1997
    Co-Authors: Anindya Dutta, Stephen P Bell
    Abstract:

    ▪ Abstract The recent identification of proteins that recognize origins of DNA Replication and control the initiation of eukaryotic DNA Replication has provided critical molecular tools to dissect this process. Dynamic changes in the assembly and disassembly of protein complexes at origins are important for the initiation of DNA Replication and occur throughout the cell cycle. Herein, we review the key proteins required for the initiation of DNA Replication, their involvement in the protein complex assembly at Replication origins, and how the cell cycle machinery regulates this process.

  • Inhibition of DNA Replication factor RPA by p53
    Nature, 1993
    Co-Authors: Anindya Dutta, J. M. Ruppert, Jon C. Aster, E. Winchester
    Abstract:

    THE tumour suppressor p53 specifically interferes with the onset of S phase. The mechanism of the growth suppression action of the protein is unclear, though recent evidence points to transcriptional activation and repression functions of the protein1. A competing hypothesis suggests that p53 interacts with the DNA Replication apparatus and directly interferes with DNA Replication. The major evidence for this hypothesis is that p53 interacts with the simian virus 40 (SV40)-encoded protein T antigen and interferes with the ability of T antigen to unwind the SV40 origin of DNA Replication, and recruit DNA polymerase α to the Replication initiation complex2,3. Here we report that p53 physically interacts with and inhibits the function of a cellular DNA Replication factor, the single-stranded DNA-binding protein complex RPA.