SUMMARY Geminiviruses constitute a large family of plant-infecting viruses with small, single-stranded DNA genomes that replicate through double-stranded intermediates. Because of their limited coding capacity, geminiviruses supply only the factors required to initiate their replication and use plant nuclear DNA polymerases to amplify their genomes. Many geminiviruses replicate in differentiated cells that no longer contain detectable levels of host DNA polymerases and associated factors. To overcome this barrier, geminiviruses induce the accumulation of DNA replication machinery in mature plant cells by reprogramming host gene expression. The mammalian DNA tumour viruses activate host genes required for DNA replication by binding to the retinoblastoma protein, a negative regulator of cell cycle progression, and relieving repression through the E2F family of transcription factors. In this review, we discuss recent experiments showing that geminiviruses also modulate components of the retinoblastoma/E2F transcription regulatory network to induce quiescent plant cells to re-enter the cell cycle and regain the capacity to support high levels of DNA replication. Regulation of the cell division cycle and its integration with developmental pathways is complex, with many factors, including hormones, sucrose and environmental signals, controlling re-entry into the plant cell cycle. Geminivirus interactions with these regulatory networks are likely to determine if and where they can replicate their genomes in different plant tissues and hosts.
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http://dx.doi.org/10.1111/j.1364-3703.2004.00214.x | DOI Listing |
Breast Cancer Res
January 2025
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, 246 Clayton Road, Clayton, VIC, 3168, Australia.
Background: Tumour DNA methylation has been investigated as a potential marker for breast cancer survival, but findings often lack replication across studies.
Methods: This study sought to replicate previously reported associations for individual CpG sites and multi-CpG signatures using an Australian sample of 425 women with breast cancer from the Melbourne Collaborative Cohort Study (MCCS). Candidate methylation sites (N = 22) and signatures (N = 3) potentially associated with breast cancer survival were identified from five prior studies that used The Cancer Genome Atlas (TCGA) methylation dataset, which shares key characteristics with the MCCS: comparable sample size, tissue type (formalin-fixed paraffin-embedded; FFPE), technology (Illumina HumanMethylation450 array), and participant characteristics (age, ancestry, and disease subtype and severity).
Clin Epigenetics
January 2025
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, 2308, Australia.
Background: Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome. HMAs act in a replication-dependent manner to remove DNA methylation from the genome. However, AML cells targeted by HMA therapy are often quiescent within the bone marrow, where oxygen levels are low.
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January 2025
Sexually Transmitted and Bloodborne Infections Surveillance and Molecular Epidemiology, Sexually Transmitted and Bloodborne Infections Division at the JC Wilt Infectious Diseases Research Centre, National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, MB, R3E 3L5, Canada.
Human Immunodeficiency Virus Type 1 (HIV) set-point viral load is a strong predictor of disease progression and transmission risk. A recent genome-wide association study in individuals of African ancestries identified a region on chromosome 1 significantly associated with decreased HIV set-point viral load. Knockout of the closest gene, CHD1L, enhanced HIV replication in vitro in myeloid cells.
View Article and Find Full Text PDFNPJ Precis Oncol
January 2025
Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Pancreatic ductal adenocarcinoma (PDAC) is notably resistant to conventional chemotherapy and radiation treatment. However, clinical trials indicate that carbon ion radiotherapy (CIRT) with concurrent gemcitabine is effective for unresectable locally advanced PDAC. This study aimed to identify patient characteristics predictive of CIRT response.
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.
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