Research Topics
Genomes and Genes | Stephen P BellSummaryAffiliation: Massachusetts Institute of Technology Country: USA Publications
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Publications
Orc6 is required for dynamic recruitment of Cdt1 during repeated Mcm2-7 loadingShuyan Chen
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Genes Dev 21:2897-907. 2007..Interestingly, this complex can only perform a single round of Mcm2-7 loading, suggesting that a dynamic association of Cdt1 with ORC is required for multiple rounds of Mcm2-7 loading...
The origin recognition complex: from simple origins to complex functionsStephen P Bell
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Genes Dev 16:659-72. 2002- DNA replication in eukaryotic cellsStephen P Bell
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA
Annu Rev Biochem 71:333-74. 2002..We emphasize recent progress in determining the function of the different replication factors once they have been assembled at the origin... - Multiple Cdt1 molecules act at each origin to load replication-competent Mcm2-7 helicasesThomas J Takara
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
EMBO J 30:4885-96. 2011.... - Mec1 is one of multiple kinases that prime the Mcm2-7 helicase for phosphorylation by Cdc7John C W Randell
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Mol Cell 40:353-63. 2010..These findings identify regulatory mechanisms that modulate origin firing and replication fork assembly during cell cycle progression... - Incorporation into the prereplicative complex activates the Mcm2-7 helicase for Cdc7-Dbf4 phosphorylationLaura I Francis
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Genes Dev 23:643-54. 2009.... - CDK prevents Mcm2-7 helicase loading by inhibiting Cdt1 interaction with Orc6Shuyan Chen
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Genes Dev 25:363-72. 2011.... - Separation of DNA replication from the assembly of break-competent meiotic chromosomesHannah G Blitzblau
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
PLoS Genet 8:e1002643. 2012..The functional separation of these processes reveals a modular method of building meiotic chromosomes and predicts that any crosstalk between these modules must occur through superimposed regulatory mechanisms... - Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicaseJohn C W Randell
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Mol Cell 21:29-39. 2006..Importantly, these coordinated yet distinct functions of ORC and Cdc6 ensure the correct temporal and spatial regulation of pre-RC formation... - Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinasesRyan C Heller
Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
Cell 146:80-91. 2011..Our studies identify distinct roles for DDK and S-CDK during helicase activation and support a model in which the leading strand DNA polymerase is recruited prior to origin DNA unwinding and RNA primer synthesis... - Dynamics of pre-replicative complex assemblyVasiliki Tsakraklides
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Biol Chem 285:9437-43. 2010..This dissociation requires ATP hydrolysis at a late stage of pre-RC assembly. Our results indicate that pre-RC formation is a dynamic process... - ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replicationJayson L Bowers
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Mol Cell 16:967-78. 2004.... - Interaction of the S-phase cyclin Clb5 with an "RXL" docking sequence in the initiator protein Orc6 provides an origin-localized replication control switchGwendolyn M Wilmes
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Genes Dev 18:981-91. 2004..We propose that Clb5 binding to ORC provides an origin-localized replication control switch that specifically prevents reinitiation at replicated origins... - Genome-wide analysis of re-replication reveals inhibitory controls that target multiple stages of replication initiationRobyn E Tanny
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Mol Biol Cell 17:2415-23. 2006..Our findings allow us to categorize origins with respect to their propensity to reinitiate and demonstrate that pre-RC formation is not the only target for the mechanisms that prevent genomic re-replication... 
Putting two heads together to unwind DNAThomas J Takara
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Cell 139:652-4. 2009..Remus et al. (2009) provide important insights into helicase loading in eukaryotes, showing that the Mcm2-7 replicative helicase encircles double-stranded DNA as head-to-head double hexamers...- Coordination of replication and transcription along a Drosophila chromosomeDavid M MacAlpine
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02319, USA
Genes Dev 18:3094-105. 2004..Based on these findings, we suggest that the distribution of transcription along the chromosome acts locally to influence origin selection and globally to regulate origin activation... - The B2 element of the Saccharomyces cerevisiae ARS1 origin of replication requires specific sequences to facilitate pre-RC formationGwendolyn M Wilmes
Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Proc Natl Acad Sci U S A 99:101-6. 2002..The function of these mutant sequences is rescued by Cdc6p overexpression. We propose that the B2 element requires specific sequences to bind a component of the pre-RC... - Visualization of replication initiation and elongation in DrosophilaJulie M Claycomb
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
J Cell Biol 159:225-36. 2002.... - Cell-cycle control of the establishment of mating-type silencing in S. cerevisiaeAnna Lau
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Genes Dev 16:2935-45. 2002..Our findings reveal both S- and M-phase requirements for the establishment of silencing and implicate the loss of sister-chromatid cohesion as a critical event in this process... - A genomic view of eukaryotic DNA replicationDavid M MacAlpine
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Chromosome Res 13:309-26. 2005..In addition to the insights they have provided already, microarray-based replication assays combined with genetic analysis will provide a powerful new approach to define the mechanisms that regulate replication origin function... - Mapping of meiotic single-stranded DNA reveals double-stranded-break hotspots near centromeres and telomeresHannah G Blitzblau
Department of Biology, Howard Hughes Medical Institute, Cambridge, Massachusetts 02139, USA
Curr Biol 17:2003-12. 2007..At least two levels of regulation govern crossover distribution: where the initiating DNA double-strand breaks (DSBs) occur and whether those DSBs are repaired as crossovers... - The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryoteDirk Schübeler
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
Genes Dev 18:1263-71. 2004..Furthermore, the degree of modification correlates with the level of transcription, and modifications are largely restricted to transcribed regions, suggesting that their regulation is tightly linked to polymerase activity... - Mapping subunit location on the Saccharomyces cerevisiae origin recognition complex free and bound to DNA using a novel nanoscale biopointerPaul D Chastain
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA
J Biol Chem 279:36354-62. 2004..This versatile, new approach to mapping protein structure has potential for many applications... - Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiaeDaniel G Gibson
Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089 2910, USA
Genes Cells 11:557-73. 2006..We discuss the potential significance of these overlapping checkpoints and the impact of our findings on previously postulated role(s) of ORCs in other cell cycle functions... - Subunit organization of Mcm2-7 and the unequal role of active sites in ATP hydrolysis and viabilityMatthew L Bochman
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
Mol Cell Biol 28:5865-73. 2008..Our conclusions predict a structural discontinuity between Mcm2 and Mcm5 and demonstrate that in contrast to other hexameric helicases, the six Mcm2-7 active sites are functionally distinct... - Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cellsDaphne Georlette
Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California 94720, USA
Genes Dev 21:2880-96. 2007.... - Localized H3K36 methylation states define histone H4K16 acetylation during transcriptional elongation in DrosophilaOliver Bell
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse, Basel, Switzerland
EMBO J 26:4974-84. 2007..Thus di- and trimethylation of H3K36 have opposite effects on H4K16 acetylation, which we propose enable dynamic changes in chromatin compaction during transcript elongation...
Research Grants
- INITIATION OF DNA REPLICATION OF YEAST CHROMOSOMESStephen P Bell; Fiscal Year: 2010..The findings will provide fundamentally important information that will be relevant to the proliferation of all animal cells including humans. ..
- INITIATION OF DNA REPLICATION OF YEAST CHROMOSOMESStephen Bell; Fiscal Year: 2003....
- INITIATION OF DNA REPLICATION OF YEAST CHROMOSOMESStephen Bell; Fiscal Year: 2007....
- Pre-Doctoral Grant in the Biological SciencesStephen Bell; Fiscal Year: 2007..Our graduate students play major roles in the intellectual life and research efforts of the Department and go on to make substantive contributions to modern biology. ..
- MCM PROTEIN FUNCTION DURING EUKARYOTIC DNA REPLICATIONStephen Bell; Fiscal Year: 2002....
- INITIATION OF DNA REPLICATION OF YEAST CHROMOSOMESStephen Bell; Fiscal Year: 1999..Second, an understanding DNA replication and its regulation in yeast will provide new targets for the development of anti-fungal drugs and therapies. ..