Eukaryotic cells are often exposed to fluctuations in growth conditions as well as endogenous and exogenous stress-related agents. During development, global patterns of gene transcription change substantially, and these changes are associated with altered patterns of DNA replication and larger distances between replication origins in somatic cells compared to embryos. Conversely, when cells experience difficulties while replicating DNA, the replication program is dramatically altered and distances between replication origins decrease. Recent evidence indicates that each unit of replication, or replicon, can correspond to one or more potential replication origins, but in the case of multiple potential origins, only one is selected to initiate replication of the replicon. How one origin is selected from multiple potential origins and how origin densities are regulated during genome duplication remains unclear. The following review addresses some of the mechanisms involved in regulating replication origins during both a normal and perturbed eukaryotic cell cycle.
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http://dx.doi.org/10.1002/bies.200900129 | DOI Listing |
Elife
January 2025
Translational Science and Therapeutics Division, Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States.
The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well known, yet the specific mechanisms underlying this link remain uncertain. In , the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA (rDNA) arrays. We have previously reported that in the absence of , a de-repressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy.
View Article and Find Full Text PDFThe six subunit Origin Recognition Complex (ORC) is a DNA replication initiator that also promotes heterochromatinization in some species. A multi-omics study in a human cell line with mutations in three subunits of ORC, reveals that the subunits bind to DNA independent of each other rather than as part of a common six-subunit ORC. While DNA-bound ORC2 was seen to compact chromatin and attract repressive histone marks, the activation of chromatin and protection from repressive marks was seen at a large number of sites.
View Article and Find Full Text PDFVirology
December 2024
Virginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, VA, 23298, USA; VCU Massey Cancer Center, Richmond, VA, 23298, USA.
All papillomaviruses encode an E2 protein and it is essential for the viral life cycle. E2 has three domains; a carboxyl-terminal DNA binding and dimerization domain, an amino-terminal protein interaction domain and a hinge region linking these two. Following homo-dimerization human papillomavirus E2 binds to four 12bp palindromic DNA sequences located in the non-coding long control region (LCR) of the viral genome.
View Article and Find Full Text PDFNat Commun
January 2025
Macromolecular Machines Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
The MCM motor of the eukaryotic replicative helicase is loaded as a double hexamer onto DNA by the Origin Recognition Complex (ORC), Cdc6, and Cdt1. ATP binding supports formation of the ORC-Cdc6-Cdt1-MCM (OCCM) helicase-recruitment complex where ORC-Cdc6 and one MCM hexamer form two juxtaposed rings around duplex DNA. ATP hydrolysis by MCM completes MCM loading but the mechanism is unknown.
View Article and Find Full Text PDFJACC Case Rep
January 2025
Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Anomalous aortic origin of coronary artery can lead to ischemia. Due to the limitations of invasive catheterization dobutamine stress testing, an alternative noninvasive approach is desired. A 65-year-old woman with atypical chest pain was referred for coronary computed tomography angiography.
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