A5004566603- DNA Repair Mechanisms
- History and Developments in Astronomy
- Soil Moisture and Remote Sensing
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Underwater Acoustics Research
- Plant Genetic and Mutation Studies
- Australian History and Society
- PARP inhibition in cancer therapy
- Rangeland and Wildlife Management
- Synthetic Aperture Radar (SAR) Applications and Techniques
- Carcinogens and Genotoxicity Assessment
- Fungal and yeast genetics research
- Advanced SAR Imaging Techniques
- Scottish History and National Identity
- Cell death mechanisms and regulation
- Water Quality Monitoring Technologies
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Ultrasonics and Acoustic Wave Propagation
University of Dundee
2016-2025
MRC Protein Phosphorylation and Ubiquitylation Unit
2016-2025
Wellcome Trust
2005-2024
Medical Research Council
2004-2016
Nirma (India)
2012
The Gurdon Institute
2002
University of Cambridge
2000-2002
St Vincent's Hospital Sydney
1999
University College London
1999
New England Biolabs (United States)
1996
Holliday junctions (HJs) are X-shaped DNA structures that arise during homologous recombination, which must be removed to enable chromosome segregation. The SLX1 and MUS81-EME1 nucleases can both process HJs in vitro, they bind close proximity on the SLX4 scaffold, hinting at possible cooperation. However, cellular roles of mammalian not yet known. Here, we use mouse genetics structure function analysis investigate function. Disrupting murine Slx1 Slx4 genes revealed essential for HJ...
Mono-ubiquitination of Fancd2 is essential for repairing DNA interstrand cross-links (ICLs), but the underlying mechanisms are unclear. The Fan1 nuclease, also required ICL repair, recruited to ICLs by ubiquitinated (Ub) Fancd2. This could in principle explain how Ub-Fancd2 promotes we show that recruitment dispensable repair. Instead, recruitment--and activity--restrains replication fork progression and prevents chromosome abnormalities from occurring when forks stall, even absence ICLs....
ATM (ataxia-telangiectasia mutated), ATR (ATM- and Rad3-related) DNA-PK (DNA-dependent protein kinase), important regulators of genome stability, belong to the PIKK (phosphoinositide 3-kinase-like kinase) family kinases. In present study, DNA-affinity chromatography was used identify DNA-binding proteins phosphorylated by these This resulted in identification FUS (fused sarcoma)/TLS (translocated liposarcoma) as an vitro target PIKKs. is a member Ewing's sarcoma that appears play role...
Human (h)PTIP plays important but poorly understood roles in cellular responses to DNA damage. hPTIP interacts with 53BP1 tumour suppressor only when is phosphorylated by ATM after damage although the mechanism(s) and significance of interaction these two proteins are unclear. Here, we pinpoint a single ATM-phosphorylated residue 53BP1--Ser25--that required for binding hPTIP. Binding phospho-Ser25 vitro vivo requires closely apposed pairs BRCT domains at C-terminus neither pair alone can...
A unique set of radiometer measurements is presented, recorded during a 1000-h day and night monitoring irrigated fields from fully saturated to completely dry. Radiometer were at 2.8-cm ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X</tex> -band) 21.4-cm xmlns:xlink="http://www.w3.org/1999/xlink">L</tex> wavelengths for range incident angles nadir xmlns:xlink="http://www.w3.org/1999/xlink">50\deg</tex> . Soil moisture soil temperature...
SLX4, a scaffold for structure-specific DNA repair nucleases, is important several types of repair. Many proteins bind to sites damage, resulting in subnuclear "foci," but SLX4 forms foci human cells even without damage. Using approaches, we show that most, not all, localize telomeres range cell lines irrespective the mechanisms used maintain telomere length. The SLX1 Holliday-junction-processing enzyme recruited by and turn, motif binds shelterin subunit TRF2 directly. We also...
Mutations in the gene encoding protein kinase CDKL5 cause a debilitating neurodevelopmental disease termed disorder. The impact of these mutations on function is poorly understood because substrates and cellular processes controlled by are unclear. Here, we describe quantitative phosphoproteomic screening which identified MAP1S, CEP131 DLG5-regulators microtubule centrosome function-as CDKL5. Antibodies against MAP1S phospho-Ser900 phospho-Ser35 confirmed CDKL5-dependent phosphorylation...
Defects in the repair of DNA interstrand crosslinks (ICLs) are associated with genome instability syndrome Fanconi anemia (FA). Here we report that cells mutations RFWD3, an E3 ubiquitin ligase interacts and ubiquitylates replication protein A (RPA), show profound defects ICL repair. An amino acid substitution WD40 repeats RFWD3 (I639K) found a new FA subtype abolishes interaction RPA, thereby preventing recruitment to sites ICL-induced fork stalling. Moreover, single point RPA32 subunit RPA...
The identities of the upstream activators mitogen‐activated protein (MAP) kinase homologues termed stress‐activated‐protein (SAP) kinase‐I (also known as JNK or SAPK) and SAP kinase‐2 p38, RK CSBP) were investigated in rat PC12 cells human KB after exposure to cellular stresses cytokines. In cells, same two activators, (SAPKK‐1) SAPKK‐2 activated osmotic shock, ultraviolet irradiation synthesis inhibitor anisomycin, more weakly response sodium arsenite. SAPKK‐1 was capable activating both...
Budding yeast (Saccharomyces cerevisiae) Slx4 is essential for cell viability in the absence of Sgs1 helicase and recovery from DNA damage. Here we report that cells lacking have difficulties completing synthesis during replisome stalling induced by alkylating agent methyl methanesulfonate (MMS). Although restarts recovery, are left with unreplicated gaps genome despite an increase translesion synthesis. In this light, epistasis experiments show SLX4 interacts genes involved error-free...