Search Results - "Botchan, Michael R."
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Mechanisms for initiating cellular DNA replication
Published in Science (American Association for the Advancement of Science) (24-02-2017)“…Cellular DNA replication factories depend on ring-shaped hexameric helicases to aid DNA synthesis by processively unzipping the parental DNA helix. Replicative…”
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Mechanisms and regulation of DNA replication initiation in eukaryotes
Published in Critical reviews in biochemistry and molecular biology (01-04-2017)“…Cellular DNA replication is initiated through the action of multiprotein complexes that recognize replication start sites in the chromosome (termed origins)…”
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Crystal structure of the eukaryotic origin recognition complex
Published in Nature (London) (19-03-2015)“…Initiation of cellular DNA replication is tightly controlled to sustain genomic integrity. In eukaryotes, the heterohexameric origin recognition complex (ORC)…”
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Zelda binding in the early Drosophila melanogaster embryo marks regions subsequently activated at the maternal-to-zygotic transition
Published in PLoS genetics (01-10-2011)“…The earliest stages of development in most metazoans are driven by maternally deposited proteins and mRNAs, with widespread transcriptional activation of the…”
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Stalled Fork Rescue via Dormant Replication Origins in Unchallenged S Phase Promotes Proper Chromosome Segregation and Tumor Suppression
Published in Molecular cell (04-03-2011)“…Eukaryotic cells license far more origins than are actually used for DNA replication, thereby generating a large number of dormant origins. Accumulating…”
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The structural basis for MCM2-7 helicase activation by GINS and Cdc45
Published in Nature structural & molecular biology (01-04-2011)“…In eukaryotes, DNA replication depends on loading the ring-shaped helicase, Mcm2–7 onto double-stranded DNA and subsequent activation by GINS–Cdc45. Using…”
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A new class of disordered elements controls DNA replication through initiator self-assembly
Published in eLife (27-09-2019)“…The initiation of DNA replication in metazoans occurs at thousands of chromosomal sites known as origins. At each origin, the Origin Recognition Complex (ORC),…”
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Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase
Published in Proceedings of the National Academy of Sciences - PNAS (05-07-2006)“…The protein Cdc45 plays a critical but poorly understood role in the initiation and elongation stages of eukaryotic DNA replication. To study Cdc45's function…”
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Molecular Basis for ATP-Hydrolysis-Driven DNA Translocation by the CMG Helicase of the Eukaryotic Replisome
Published in Cell reports (Cambridge) (03-09-2019)“…In the eukaryotic replisome, DNA unwinding by the Cdc45-MCM-Go-Ichi-Ni-San (GINS) (CMG) helicase requires a hexameric ring-shaped ATPase named minichromosome…”
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Conformational control and DNA-binding mechanism of the metazoan origin recognition complex
Published in Proceedings of the National Academy of Sciences - PNAS (26-06-2018)“…In eukaryotes, the heterohexameric origin recognition complex (ORC) coordinates replication onset by facilitating the recruitment and loading of the…”
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Cdc45 (cell division cycle protein 45) guards the gate of the Eukaryote Replisome helicase stabilizing leading strand engagement
Published in Proceedings of the National Academy of Sciences - PNAS (20-01-2015)“…DNA replication licensing is now understood to be the pathway that leads to the assembly of double hexamers of minichromosome maintenance (Mcm2–7) at origin…”
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ATP-dependent conformational dynamics underlie the functional asymmetry of the replicative helicase from a minimalist eukaryote
Published in Proceedings of the National Academy of Sciences - PNAS (24-07-2012)“…The heterohexameric minichromosome maintenance (MCM2–7) complex is an ATPase that serves as the central replicative helicase in eukaryotes. During initiation,…”
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Molecular determinants of phase separation for Drosophila DNA replication licensing factors
Published in eLife (24-12-2021)“…Liquid-liquid phase separation (LLPS) of intrinsically disordered regions (IDRs) in proteins can drive the formation of membraneless compartments in cells…”
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Grainyhead and Zelda compete for binding to the promoters of the earliest-expressed Drosophila genes
Published in Developmental biology (15-09-2010)“…Maternally contributed mRNAs and proteins control the initial stages of development following fertilization. During this time, most of the zygotic genome…”
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DNA binding polarity, dimerization, and ATPase ring remodeling in the CMG helicase of the eukaryotic replisome
Published in eLife (12-08-2014)“…The Cdc45/Mcm2-7/GINS (CMG) helicase separates DNA strands during replication in eukaryotes. How the CMG is assembled and engages DNA substrates remains…”
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Checkpoint kinase 2 (Chk2) inhibits the activity of the Cdc45/MCM2-7/GINS (CMG) replicative helicase complex
Published in Proceedings of the National Academy of Sciences - PNAS (14-08-2012)“…The replication of eukaryote chromosomes slows down when DNA is damaged and the proteins that work at the fork (the replisome) are known targets for the…”
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Chromatin reader L(3)mbt requires the Myb–MuvB/DREAM transcriptional regulatory complex for chromosomal recruitment
Published in Proceedings of the National Academy of Sciences - PNAS (07-10-2014)“…Lethal malignant brain tumors (lmbt) result from the loss of the conserved transcriptional repressor l(3)mbt, in Drosophila melanogaster. Similar mutations in…”
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Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells
Published in Genes & development (15-11-2007)“…Myb-MuvB (MMB)/dREAM is a nine-subunit complex first described in Drosophila as a repressor of transcription, dependent on E2F2 and the RBFs. Myb, an integral…”
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A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes origin recognition complex formation
Published in eLife (08-10-2013)“…In eukaryotes, DNA replication requires the origin recognition complex (ORC), a six-subunit assembly that promotes replisome formation on chromosomal origins…”
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Activation of the MCM2-7 Helicase by Association with Cdc45 and GINS Proteins
Published in Molecular cell (29-01-2010)“…MCM2-7 proteins provide essential helicase functions in eukaryotes at chromosomal DNA replication forks. During the G1 phase of the cell cycle, they remain…”
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