A5073544703- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Fungal and yeast genetics research
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Palliative Care and End-of-Life Issues
- Epigenetics and DNA Methylation
- Chromosomal and Genetic Variations
- Genetics and Neurodevelopmental Disorders
- Cancer-related Molecular Pathways
- DNA and Nucleic Acid Chemistry
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Interprofessional Education and Collaboration
- Nuclear Structure and Function
- Geriatric Care and Nursing Homes
- Cancer Genomics and Diagnostics
- Grief, Bereavement, and Mental Health
- Chronic Disease Management Strategies
- Health Systems, Economic Evaluations, Quality of Life
- Bacterial Genetics and Biotechnology
- Patient Dignity and Privacy
- Plant Disease Resistance and Genetics
University of Aberdeen
2015-2025
Institute of Medical Sciences
2005-2022
Donaldson (United States)
2017
University of Edinburgh
2010-2014
Queen Mary University of London
2013
Cicely Saunders International
2013
Primary Health Care
2013
University of Warwick
2013
King's College London
2013
University of Cambridge
2013
Initiation of eukaryotic DNA replication requires phosphorylation the MCM complex by Dbf4-dependent kinase (DDK), composed Cdc7 and its activator, Dbf4. We report here that budding yeast Rif1 (Rap1-interacting factor 1) controls genome-wide describe how opposes DDK function directing Protein Phosphatase 1 (PP1)-mediated dephosphorylation complex. Deleting RIF1 partially compensates for limited activity in a cdc7-1 mutant strain allowing increased, premature Mcm4. PP1 interaction motifs...
Replication timing organizes epigenome The temporal order of DNA replication is conserved from yeast to humans, but its biological significance remains unclear. Klein et al. eliminated the protein RIF1, a master regulator timing, in several human cell lines. RIF1 loss during G1 phase cycle resulted heterogeneous, nearly random program first S that persisted even stable RIF1-null clones. Altered was followed by replication-dependent redistribution active and repressive histone modifications...
Anne D. Donaldson, Walton L. Fangman, and Bonita J. Brewer Department of Genetics, University Washington, Seattle, Washington 98195-7360 USA
We discovered that sequences essential for replication origin function are frequently conserved in sensu stricto Saccharomyces species. Here we use analysis of phylogenetic conservation to identify throughout the cerevisiae genome at base pair resolution. Origin activity was confirmed each 228 predicted sites—representing 86% apparent regions. This is first study determine genome-wide location origins a resolution sufficient sequence elements bound by proteins. Our results demonstrate can be...
Replication of eukaryotic chromosomes initiates at multiple sites called replication origins. origins are best understood in the budding yeast Saccharomyces cerevisiae, where several complementary studies have mapped their locations genome-wide. We collated these datasets, taking account resolution each study, to generate a single list distinct origin sites. OriDB provides web-based catalogue confirmed and predicted S.cerevisiae DNA Each proposed or site appears as record OriDB, with...
Article11 January 2017Open Access Transparent process Human RIF1 and protein phosphatase 1 stimulate DNA replication origin licensing but suppress activation Shin-ichiro Hiraga Corresponding Author [email protected] orcid.org/0000-0002-8722-3869 Institute of Medical Sciences, School Medicine, Sciences & Nutrition, University Aberdeen, UK Search for more papers by this author Tony Ly Centre Gene Regulation Expression, Life Dundee, Javier Garzón Zuzana Hořejší The Francis Crick Institute,...
The sliding clamp PCNA is a crucial component of the DNA replication machinery. Timely loading and unloading are central for genome integrity must be strictly coordinated with other processing steps during replication. Here, we show that S. cerevisiae Elg1 factor C-like complex (Elg1-RLC) unloads genome-wide following Okazaki fragment ligation. In absence Elg1, retained on chromosomes in wake forks, rather than at specific sites. Degradation ligase Cdc9 leads to accumulation chromatin,...
The 42-kD component of the S. cerevisiae spindle pole body (SPB) localizes to electron-dense central plaque SPB. We have cloned corresponding gene SPC42 (spindle component) and show that it is essential. Seven temperature-sensitive (ts) mutants in were prepared by error-prone PCR. found a change proline residue potential coiled-coil region Spc42p was responsible for ts phenotype at least three alleles, suggesting formation essential normal function. mutant cells showed predominantly single...
Objective Multimorbidity is increasingly common in the last year of life, and associated with frequent hospital admissions. The epidemiology well described, but patient perspectives are less understood. We report experiences perceptions people advanced multimorbidity to inform improvements palliative end-of-life care. Design Multicentre study including serial, multiperspective interviews patients their family carers; an interpretive analysis understanding living multimorbidity. Participants...
RIF1 is a multifunctional protein implicated in controlling DNA replication and repair. Here, we show that human protects nascent from over-degradation at stalled forks. The major nuclease resecting the absence of DNA2, operating with WRN as an accessory helicase. We acts phosphatase 1 to prevent limits phosphorylation sites resection control. Protection by against inappropriate degradation prevents accumulation breakage. Our observations uncover crucial function preventing genome...
ABSTRACT We have expressed in Escherichia coli cDNA corresponding to human lamins A and C, together with a number of fragments produced using site-specific mutagenesis. The proteins this way were characterised both biochemically ultrastructurally, appeared retain their native conformation. Crosslinking showed that all formed 4-chain molecular dimers (‘tetramers’) analogous those by intact intermediate filament proteins. Shadowed preparations the presence rod-like particles closely resembled...
Objectives To develop a model of care coordination for patients living with advanced progressive illness and their unpaid caregivers, to understand perspective regarding coordination. Design A prospective longitudinal, multi-perspective qualitative study involving case-study approach. Methods Serial in-depth interviews were conducted, transcribed verbatim then analyzed through open axial coding in order construct categories three cases (sites). This was followed by continued thematic...
DNA replication in Saccharomyces cerevisiae proceeds according to a temporal program. We have investigated the role of telomere-binding Ku complex specifying late telomere-proximal sequences. Genome-wide analysis shows that regions extending up 80 kb from telomeres replicate abnormally early yku70 mutant. find does not appear regulate time by binding origins directly, nor is its effect on telomere timing mediated histone tail acetylation. show instead regulates through length, because...
Yeast cells lacking Ctf18, the major subunit of an alternative Replication Factor C complex, have multiple problems with genome stability. To understand in vivo function Ctf18 we analyzed chromatin composition a ctf18Δ mutant using quantitative proteomic technique stable isotope labeling by amino acids cell culture. Three hundred and seven 491 reported chromosomal proteins were quantitated. The most marked abnormalities occurred when challenged replication inhibitor hydroxyurea. Compared...
Coordination of care for individuals with advanced progressive conditions is frequently poor.To identify how coordinated in generalist settings the last year life.A mixed methods study three UK clinical producing parallel case studies: an acute admissions unit a regional hospital, large general practice, and respiratory outpatient service.Ethnographic observations each setting, followed by serial interviews patients their family carers community. A spectrum clinicians healthcare workers were...
RIF1 is a multifunctional protein that regulates DNA replication and repair. RIF1-deficient cells are hypersensitive to stress. Of the two alternatively spliced isoforms, called RIF1-Short RIF1-Long, RIF1-Long isoform more capable than in supporting cell recovery from Examining stress resistance mechanisms specific we find prolonged unexpectedly induces interaction of with BRCA1. Mechanistically, phosphorylated SPKF motif unique binds tandem BRCT domain BRCA1-RIF1-Long strongly...
We have investigated whether the Ku complex is involved in regulating DNA replication yeast Saccharomyces cerevisiae . find that proteins control time of telomeric regions; origins located close to telomeres or within subtelomeric repeat sequences normally initiate late, but are activated much earlier mutants lacking function. In contrast, distant from at normal time. one first components identified as important for timing, and specification chromosome ends by consistent with its role...