A5080856497- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Fungal and yeast genetics research
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Origins and Evolution of Life
- Carcinogens and Genotoxicity Assessment
- Microtubule and mitosis dynamics
- Evolution and Genetic Dynamics
- Fungal Biology and Applications
- Bacterial Genetics and Biotechnology
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- bioluminescence and chemiluminescence research
- Fermentation and Sensory Analysis
- Peptidase Inhibition and Analysis
- Cancer Genomics and Diagnostics
- Retinal Development and Disorders
- Advanced Thermodynamics and Statistical Mechanics
- Gene Regulatory Network Analysis
- Genetics, Aging, and Longevity in Model Organisms
- Trace Elements in Health
- Connexins and lens biology
- thermodynamics and calorimetric analyses
Japanese Foundation For Cancer Research
2022-2025
Tohoku University
2007-2023
Cancer Research UK
2008-2018
University of Sussex
2012-2017
Kyushu University
2016
Frontier Science Foundation
2015
Replicative DNA damage bypass, mediated by the ubiquitylation of sliding clamp protein PCNA, facilitates survival a cell in presence genotoxic agents, but it can also promote genomic instability damage-induced mutagenesis. We show here that PCNA budding yeast is activated independently replication-dependent S phase checkpoint similar conditions involving accumulation single-stranded at stalled replication intermediates. The ssDNA-binding A (RPA), an essential complex involved most...
Article26 March 2018Open Access Source DataTransparent process Spatial separation between replisome- and template-induced replication stress signaling Néstor García-Rodríguez orcid.org/0000-0002-4049-1604 Institute of Molecular Biology (IMB), Mainz, Germany Search for more papers by this author Magdalena Morawska Cancer Research UK London Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Ronald P Wong orcid.org/0000-0002-4652-514X Yasukazu Daigaku Helle D Ulrich Corresponding...
Abstract The division of labour among DNA polymerase underlies the accuracy and efficiency replication. However, roles replicative polymerases have not been directly established in human cells. We developed usage sequencing (Pu-seq) HCT116 cells mapped Polε Polα genome wide. profiles show synthesises leading strand contributes mainly to lagging synthesis. Combining profiles, we accurately predict genome-wide pattern fork directionality plus zones replication initiation termination. confirm...
Secretory pathway Ca2+/Mn2+ ATPase 1 (SPCA1) actively transports cytosolic Ca2+ and Mn2+ into the Golgi lumen, playing a crucial role in cellular calcium manganese homeostasis. Detrimental mutations of ATP2C1 gene encoding SPCA1 cause Hailey-Hailey disease. Here, using nanobody/megabody technologies, we determined cryo-electron microscopy structures human SPCA1a ATP Ca2+/Mn2+-bound (E1-ATP) state metal-free phosphorylated (E2P) at 3.1- to 3.3-Å resolutions. The revealed that share same metal...
Development of single-molecule localization microscopy techniques has allowed nanometre scale accuracy inside cells, permitting the resolution ultra-fine cell structure and elucidation crucial molecular mechanisms. Application these methodologies to understanding processes underlying DNA replication repair been limited defined in vitro biochemical analysis prokaryotic cells. In order expand eukaryotic systems, we have further developed a photo-activated microscopy-based method directly...
Summary Various methods have been developed to map replication initiation zones (IZs) genome-wide, often finding far fewer IZs than expected. In particular, corresponding later stages of S phase are under-represented. Here, we re-analyzed with respect timing in mouse ES cells. These data sets identified over five times as many early compared late-IZs. addition, set up a polymerase-usage sequencing (Pu-seq) system cells genome-wide. Pu-seq showed less bias towards IZs, potentially indicating...
The retinal pigment epithelium (RPE) performs life-long phagocytosis of lipid-rich photoreceptor outer segments and exchanges energy metabolites with photoreceptors to support function. glucose lipid metabolism are interconnected, but it is unclear how the specialized RPE regulated. We have investigated this unique mechanism. To identify factors involved in regulation we compared screened human epithelial cell line, ARPE-19 under different conditions. Using results these experiments selected...
PCNA ubiquitylation on lysine 164 is required for DNA damage tolerance. In many organisms also ubiquitylated in unchallenged S phase but the significance of this has not been established. Using Schizosaccharomyces pombe, we demonstrate that contributes to efficient replication absence damage. Loss manifests most strongly at late replicating regions and increases frequency gaps. We show proportion chromatin associated co-immunoprecipitation Polymerase δ with during unperturbed propose acts...
Abstract Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is in most cases caused by mutations either DNA methyltransferase (DNMT)3B, zinc finger BTB domain containing 24, cell division cycle associated 7 or helicase lymphoid-specific. However, the causative genes of a few ICF patients remain unknown. We, herein, identified ubiquitin-like with plant homeodomain really interesting new gene domains 1 (UHRF1) as novel one such patient atypical symptoms. This...
The ability to study protein function in vivo often relies on systems that regulate the presence and absence of interest. Two limitations for previously described transcriptional control are used expression fission yeast are: time taken inducing conditions initiate transcription achieve very low basal "OFF-state". In previous work, we a Cre recombination-mediated system allows rapid efficient regulation any gene interest by urg1 promoter, which has dynamic range approximately 75-fold is...
Using the CAN1 gene in haploid cells or heterozygous diploid cells, we characterized effects of mutations RAD52 and REV3 genes Saccharomyces cerevisiae spontaneous mutagenesis. The mutation rate was 5-fold higher rad52 strain 2.5-fold lower rev3 than wild-type strain. as low strain, indicating mutator phenotype to be dependent on REV3. Sequencing indicated that G:C-->T:A G:C-->C:G transversions increased decreased strains, suggesting a role for transversion In frequencies...
Gene/segmental duplications play crucial roles in genome evolution and variation. Here, we introduce paired nicking-induced amplification (PNAmp) for their experimental induction. PNAmp strategically places two Cas9 nickases upstream downstream of a replication origin on opposite strands. This configuration directs the sister forks initiated from to break at nicks, generating pair one-ended double-strand breaks. If homologous sequences flank sites, then end resection converts them...
SUMMARY Regulation of RNA polymerase II (Pol II) transcription is closely associated with cell proliferation. However, it remains unclear how the Pol program altered in cancer to favour growth. Here, we find that gene expression NELFCD , a known negative elongation factor, up-regulated colorectal tumours. To dissect direct role NELF-C on such cancer, employed an auxin-dependent protein degradation system for combination nascent transcript sequencing technologies. Strikingly, demonstrated...
Abstract Regulation of RNA polymerase II (Pol II) transcription is closely associated with cell proliferation. However, it remains unclear how the Pol program altered in cancer to favour growth. Here, we find that gene expression NELFCD, a known negative elongation factor, up-regulated colorectal tumours. To dissect direct role NELF-C on such cancer, employed an auxin-dependent protein degradation system for combination nascent transcript sequencing technologies. Strikingly, demonstrated...