A5083750327- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Cell Adhesion Molecules Research
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Chronic Lymphocytic Leukemia Research
- PARP inhibition in cancer therapy
- Carcinogens and Genotoxicity Assessment
- Cancer Mechanisms and Therapy
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Ubiquitin and proteasome pathways
- Cancer Treatment and Pharmacology
- Signaling Pathways in Disease
- Herpesvirus Infections and Treatments
- Metalloenzymes and iron-sulfur proteins
- Mitochondrial Function and Pathology
- Immune Cell Function and Interaction
- Kruppel-like factors research
- Fungal and yeast genetics research
- Plant tissue culture and regeneration
AstraZeneca (United Kingdom)
2024
Institute of Genetics and Cancer
2015-2021
University of Edinburgh
2015-2021
Medical Research Council
2021
Western General Hospital
2018
University of Zurich
2013-2016
Russian Academy of Sciences
2014
St Petersburg University
2007-2010
The resolution of DNA interstrand crosslinks (ICLs) requires a complex interplay between several processes metabolism, including the Fanconi anemia (FA) pathway and homologous recombination (HR). FANCD2 monoubiquitination CtIP-dependent DNA-end resection represent key events in FA HR activation, respectively, but very little is known about their functional relationship. Here, we show that CtIP physically interacts with both ubiquitin monoubiquitinated tethers to damaged chromatin, which...
The regulation of DNA double-strand break (DSB) repair by phosphorylation-dependent signaling pathways is crucial for the maintenance genome stability; however, remarkably little known about molecular mechanisms which phosphorylation controls DSB repair. Here, we show that PIN1, a phosphorylation-specific prolyl isomerase, interacts with key factors and affects relative contributions homologous recombination (HR) nonhomologous end-joining (NHEJ) to We find PIN1-deficient cells display...
Long INterspersed Element class 1 (LINE-1) elements are a type of abundant retrotransposons active in mammalian genomes. An average human genome contains ~100 retrotransposition-competent LINE-1s, whose activity is influenced by the combined action cellular repressors and activators. TREX1, SAMHD1 ADAR1 known LINE-1 when mutated cause autoinflammatory disorder Aicardi-Goutières syndrome (AGS). Mutations RNase H2 most common AGS, its was proposed to similarly control retrotransposition. It...
Abstract Human CtIP is a decisive factor in DNA double-strand break repair pathway choice by enabling DNA-end resection, the first step that differentiates homologous recombination (HR) from non-homologous end-joining (NHEJ). To coordinate appropriate and timely execution of function tightly controlled multiple protein–protein interactions post-translational modifications. Here, we identify Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as new interaction partner show...
DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated human disease, and here we report PRIM1 encoding catalytic subunit primase as a novel disease gene. Using variant classification agnostic approach, biallelic mutations were identified five individuals. protein levels markedly reduced patient cells, accompanied by fork asymmetry, increased interorigin distances, stress, prolonged S-phase duration. Consequently,...
Microcephalic primordial dwarfism (MPD) is a group of rare single-gene disorders characterized by the extreme reduction in brain and body size from early development onwards. Proteins encoded MPD-associated genes play important roles fundamental cellular processes, notably genome replication repair. Here we report identification four MPD individuals with biallelic variants DNA2, which encodes an adenosine triphosphate (ATP)-dependent helicase/nuclease involved DNA We demonstrate that two...
Abstract SRC is a nonreceptor tyrosine kinase with key roles in breast cancer development and progression. Despite this, inhibitors have so far failed to live up their promise clinical trials, poor overall response rates. We aimed identify possible synergistic gene–drug interactions discover new rational combination therapies for inhibitors. An unbiased genome-wide CRISPR-Cas9 knockout screen model of triple-negative revealed that loss integrin-linked (ILK) its binding partners α-Parvin...
Abstract Background: Ceralasertib, a potent, selective ATR inhibitor, is synthetically lethal in ATM-deficient preclinical models. This Phase 2a study (NCT04564027) assessed ceralasertib monotherapy previously treated pts with ATM-altered tumors. Methods: Adult had ASTs excluding NSCLC (Cohort [Co] A; data cutoff [DCO] Dec 21 2022) or mCRPC (Co B; DCO Apr 28 2023) and germline/somatic ATM pathogenic/likely pathogenic variants (PVs) by local assessment. alterations were centrally confirmed...
In the yeast Saccharomyces cerevisiae translation termination factor eRF1 is encoded by essential gene SUP45. Here we applied multicopy library to identify a new which interacts with release in cerevisiae. We identified EСM23 whose overexpression decreased viability of sup45 nonsense mutants. also showed that ECM23 had antisuppressor effect but level protein was same as wild-type cells. The mechanisms influence mutants are discussed
<div>Abstract<p>SRC is a nonreceptor tyrosine kinase with key roles in breast cancer development and progression. Despite this, SRC inhibitors have so far failed to live up their promise clinical trials, poor overall response rates. We aimed identify possible synergistic gene–drug interactions discover new rational combination therapies for inhibitors. An unbiased genome-wide CRISPR-Cas9 knockout screen model of triple-negative revealed that loss integrin-linked (ILK) its binding...
Supplementary Data from Loss of Integrin-Linked Kinase Sensitizes Breast Cancer to SRC Inhibitors
Supplementary Data from Loss of Integrin-Linked Kinase Sensitizes Breast Cancer to SRC Inhibitors
Supplementary Data from Loss of Integrin-Linked Kinase Sensitizes Breast Cancer to SRC Inhibitors