Author
Carol S. Newlon
Other affiliations: University of Iowa, University of Medicine and Dentistry of New Jersey, University of Washington ...read more
Bio: Carol S. Newlon is an academic researcher from Rutgers University. The author has contributed to research in topics: DNA replication & Control of chromosome duplication. The author has an hindex of 41, co-authored 72 publications receiving 6396 citations. Previous affiliations of Carol S. Newlon include University of Iowa & University of Medicine and Dentistry of New Jersey.
Papers published on a yearly basis
Papers
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University of Manchester1, Leiden University2, University of Milan3, Curie Institute4, University of Paris5, University of Aberdeen6, Katholieke Universiteit Leuven7, Pasteur Institute8, Ludwig Maximilian University of Munich9, Sapienza University of Rome10, Norwich Research Park11, Université catholique de Louvain12, Université libre de Bruxelles13, University of Amsterdam14, École Normale Supérieure15, Centre national de la recherche scientifique16, Kobe University17, Trinity College, Dublin18, VU University Amsterdam19, Rutgers University20, University of Konstanz21
TL;DR: The entire DNA sequence of chromosome III of the yeast Saccharomyces cerevisiae has been determined, which is the first complete sequence analysis of an entire chromosome from any organism.
Abstract: The entire DNA sequence of chromosome III of the yeast Saccharomyces cerevisiae has been determined. This is the first complete sequence analysis of an entire chromosome from any organism. The 315-kilobase sequence reveals 182 open reading frames for proteins longer than 100 amino acids, of which 37 correspond to known genes and 29 more show some similarity to sequences in databases. Of 55 new open reading frames analysed by gene disruption, three are essential genes; of 42 non-essential genes that were tested, 14 show some discernible effect on phenotype and the remaining 28 have no overt function.
811 citations
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TL;DR: It is shown that hydroxyurea-treated rad53 mutants accumulate unusual DNA structures at replication forks, and it is proposed that Rad53 prevents collapse of the fork when replication pauses.
Abstract: In response to DNA damage and blocks to replication, eukaryotes activate the checkpoint pathways that prevent genomic instability and cancer by coordinating cell cycle progression with DNA repair. In budding yeast, the checkpoint response requires the Mec1-dependent activation of the Rad53 protein kinase. Active Rad53 slows DNA synthesis when DNA is damaged and prevents firing of late origins of replication. Further, rad53 mutants are unable to recover from a replication block. Mec1 and Rad53 also modulate the phosphorylation state of different DNA replication and repair enzymes. Little is known of the mechanisms by which checkpoint pathways interact with the replication apparatus when DNA is damaged or replication blocked. We used the two-dimensional gel technique to examine replication intermediates in response to hydroxyurea-induced replication blocks. Here we show that hydroxyurea-treated rad53 mutants accumulate unusual DNA structures at replication forks. The persistence of these abnormal molecules during recovery from the hydroxyurea block correlates with the inability to dephosphorylate Rad53. Further, Rad53 is required to properly maintain stable replication forks during the block. We propose that Rad53 prevents collapse of the fork when replication pauses.
775 citations
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TL;DR: Replication fork pause (RFP) sites transiently arresting replication fork movement were mapped to transfer RNA (tRNA) genes of Saccharomyces cerevisiae in vivo, suggesting that transcription is required for RFP activity.
Abstract: Replication fork pause (RFP) sites transiently arresting replication fork movement were mapped to transfer RNA (tRNA) genes of Saccharomyces cerevisiae in vivo. RFP sites are polar, stalling replication forks only when they oppose the direction of tRNA transcription. Mutant tRNA genes defective in assembly of transcription initiation complexes and a temperature-sensitive RNA polymerase III mutant (rpc160-41) defective in initiation of transcription do not stall replication forks, suggesting that transcription is required for RFP activity.
363 citations
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Pasteur Institute1, University of Queensland2, Duke University3, Jawaharlal Nehru Centre for Advanced Scientific Research4, Institut national de la recherche agronomique5, Yonsei University6, Rutgers University7, Washington University in St. Louis8, Broad Institute9, University of Virginia10, California Institute of Technology11, University of Missouri–Kansas City12, BC Cancer Agency13, Clemson University14, University of North Carolina at Chapel Hill15, University of Minnesota16, University of California, Riverside17, University of British Columbia18
TL;DR: The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence.
Abstract: Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence.
347 citations
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TL;DR: The past year has seen significant advances in understanding of the structure and function of yeast ARS elements, some of which function as chromosomal origins of DNA replication, are modular in structure.
239 citations
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
22,269 citations
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Université catholique de Louvain1, McGill University2, Stanford University3, Pierre-and-Marie-Curie University4, Ludwig Maximilian University of Munich5, Centre national de la recherche scientifique6, École Normale Supérieure7, Washington University in St. Louis8, John Radcliffe Hospital9, Max Planck Society10, University of Basel11, University of Manchester12
TL;DR: The genome of the yeast Saccharomyces cerevisiae has been completely sequenced through a worldwide collaboration and provides information about the higher order organization of yeast's 16 chromosomes and allows some insight into their evolutionary history.
Abstract: The genome of the yeast Saccharomyces cerevisiae has been completely sequenced through a worldwide collaboration. The sequence of 12,068 kilobases defines 5885 potential protein-encoding genes, approximately 140 genes specifying ribosomal RNA, 40 genes for small nuclear RNA molecules, and 275 transfer RNA genes. In addition, the complete sequence provides information about the higher order organization of yeast's 16 chromosomes and allows some insight into their evolutionary history. The genome shows a considerable amount of apparent genetic redundancy, and one of the major problems to be tackled during the next stage of the yeast genome project is to elucidate the biological functions of all of these genes.
4,254 citations
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TL;DR: A set of yeast strains based on Saccharomyces cerevisiae S288C in which commonly used selectable marker genes are deleted by design based on the yeast genome sequence has been constructed and analysed and will reduce plasmid integration events which can interfere with a wide variety of molecular genetic applications.
Abstract: A set of yeast strains based on Saccharomyces cerevisiae S288C in which commonly used selectable marker genes are deleted by design based on the yeast genome sequence has been constructed and analysed. These strains minimize or eliminate the homology to the corresponding marker genes in commonly used vectors without significantly affecting adjacent gene expression. Because the homology between commonly used auxotrophic marker gene segments and genomic sequences has been largely or completely abolished, these strains will also reduce plasmid integration events which can interfere with a wide variety of molecular genetic applications. We also report the construction of new members of the pRS400 series of vectors, containing the kanMX, ADE2 and MET15 genes.
3,448 citations
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TL;DR: The molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed and apoptosis, which eliminates heavily damaged or seriously deregulated cells, is analyzed.
Abstract: DNA damage is a relatively common event in the life of a cell and may lead to mutation, cancer, and cellular or organismic death. Damage to DNA induces several cellular responses that enable the cell either to eliminate or cope with the damage or to activate a programmed cell death process, presumably to eliminate cells with potentially catastrophic mutations. These DNA damage response reactions include: (a) removal of DNA damage and restoration of the continuity of the DNA duplex; (b) activation of a DNA damage checkpoint, which arrests cell cycle progression so as to allow for repair and prevention of the transmission of damaged or incompletely replicated chromosomes; (c) transcriptional response, which causes changes in the transcription profile that may be beneficial to the cell; and (d) apoptosis, which eliminates heavily damaged or seriously deregulated cells. DNA repair mechanisms include direct repair, base excision repair, nucleotide excision repair, double-strand break repair, and cross-link repair. The DNA damage checkpoints employ damage sensor proteins, such as ATM, ATR, the Rad17-RFC complex, and the 9-1-1 complex, to detect DNA damage and to initiate signal transduction cascades that employ Chk1 and Chk2 Ser/Thr kinases and Cdc25 phosphatases. The signal transducers activate p53 and inactivate cyclin-dependent kinases to inhibit cell cycle progression from G1 to S (the G1/S checkpoint), DNA replication (the intra-S checkpoint), or G2 to mitosis (the G2/M checkpoint). In this review the molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed.
3,171 citations
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TL;DR: It appears that some checkpoints are eliminated during the early embryonic development of some organisms; this fact may pose special problems for the fidelity of embryonic cell division.
Abstract: The events of the cell cycle of most organisms are ordered into dependent pathways in which the initiation of late events is dependent on the completion of early events. In eukaryotes, for example, mitosis is dependent on the completion of DNA synthesis. Some dependencies can be relieved by mutation (mitosis may then occur before completion of DNA synthesis), suggesting that the dependency is due to a control mechanism and not an intrinsic feature of the events themselves. Control mechanisms enforcing dependency in the cell cycle are here called checkpoints. Elimination of checkpoints may result in cell death, infidelity in the distribution of chromosomes or other organelles, or increased susceptibility to environmental perturbations such as DNA damaging agents. It appears that some checkpoints are eliminated during the early embryonic development of some organisms; this fact may pose special problems for the fidelity of embryonic cell division.
3,048 citations