A5034231133- DNA Repair Mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Radiation Therapy and Dosimetry
- PARP inhibition in cancer therapy
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Chemical Thermodynamics and Molecular Structure
- RNA regulation and disease
- T-cell and B-cell Immunology
- Chalcogenide Semiconductor Thin Films
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Advanced Radiotherapy Techniques
- Thermodynamic and Structural Properties of Metals and Alloys
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Cancer Cells and Metastasis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Acute Lymphoblastic Leukemia research
- Immune cells in cancer
- Fungal Infections and Studies
- Muscle Physiology and Disorders
Stanford University
2020-2024
University of Copenhagen
2014-2022
Institut Pasteur
2009-2018
Centre National de la Recherche Scientifique
2009-2018
Biologie du Développement et Cellules Souches
2013-2018
Laboratoire de Recherche Scientifique
2013
Institut Clinique de la Souris
2012
Abstract RNA-guided nucleases (RGNs) based on CRISPR systems permit installing short and large edits within eukaryotic genomes. However, precise genome editing is often hindered due to nuclease off-target activities the multiple-copy character of vast majority chromosomal sequences. Dual nicking RGNs high-specificity both exhibit low activities. Here, we report that Cas9 are convertible into Cas9D10A variants whose precision superior commonly used nickase. a selected group these can yield...
Significance Alternative end joining (A-EJ) is implicated in oncogenic translocations and mediating DNA double-strand-break (DSB) repair cycling cells when classical nonhomologous end-joining (C-NHEJ) factors of the C-NHEJ ligase complex are absent. However, V(D)J recombination-associated DSBs that occur G1 cell cycle-phase progenitor lymphocytes joined exclusively by pathway. Until now, however, overall mechanisms join general G1-phase B had not been fully elucidated. Here, we report Ku, a...
Blood cell production relies on the coordinated activities of hematopoietic stem cells (HSCs) and multipotent lineage-restricted progenitors. Here, we identify Notchless (Nle) as a critical factor for HSC maintenance under both homeostatic cytopenic conditions. Nle deficiency leads to rapid drastic exhaustion HSCs immature progenitors failure maintain quiescence in HSCs. In contrast, is dispensable cycling-restricted differentiated cells. yeast, Nle/Rsa4 essential ribosome biogenesis, show...
The contribution of basal cellular processes to the regulation tissue homeostasis has just started be appreciated. However, our knowledge modulation ribosome biogenesis activity in situ within specific lineages remains very limited. This is largely due lack assays that enable quantitation small numbers cells vivo. We used a technique, named Flow-FISH, combining cell surface antibody staining and flow cytometry with intracellular ribosomal RNA (rRNA) FISH, measure levels pre-rRNAs...
ABSTRACT Cell fate decisions occur through the action of multiple factors, including signalling molecules and transcription factors. Recently, regulation translation has emerged as an important step for modulating cellular function fate, exemplified by ribosomes that play distinct roles in regulating cell behaviour. Notchless (Nle) is a conserved nuclear protein involved crucial ribosome biogenesis, required maintenance adult haematopoietic intestinal stem/progenitor cells. Here, we show...
The molecular and cellular mechanisms driving the enhanced therapeutic ratio of ultra-high dose-rate radiotherapy (FLASH-RT) over slower conventional (CONV-RT) remain to be elucidated. However, attenuated DNA damage transient oxygen depletion are among several proposed models. Here, we tested whether FLASH-RT under physioxic (4% O 2 ) hypoxic conditions (≤2% reduces genome-wide translocations relative CONV-RT any differences identified revert normoxic (21% conditions. We employed...
Stem cells located at the apex of cellular hierarchies are responsible for maintaining intestine and colon epithelium. Similarly, that express stem cell markers have been identified in colorectal cancer, where they proposed to support growth relapse tumor.1,2 However, recently, distinct from cancer found contribute tumor distant metastasis.3,4 It is consequently pertinent understand how specific drivers, such as loss adenomatous polyposis coli (APC), affect behavior responses differentiation.
Abstract G0/G1-phase alternative end joining (A-EJ) is a recently defined mutagenic pathway characterized by resected deletion and translocation joints that are predominantly direct distinguished from A-EJ in cycling cells which rely much more on microhomology-mediated (MMEJ). Using chemical genetic approaches, we systematically evaluate potential factors DNA damage response (DDR) genes to support this mechanism mapping the repair fates of RAG1/2-initiated DSBs context Igκ locus V-J...
G 0 -G 1 phase alternative end joining (A-EJ) is a recently defined mutagenic pathway characterized by resected deletion and translocation joints that are predominantly direct distinguished from A-EJ in cycling cells rely much more on microhomology-mediated (MMEJ). Using chemical genetic approaches, we systematically evaluate potential factors DNA damage response (DDR) genes to support this mechanism mapping the repair fates of RAG1/2-initiated double-strand breaks context Igκ locus V-J...
Abstract Classical nonhomologous end-joining (C-NHEJ) repairs DNA double-stranded breaks (DSBs) throughout interphase but predominates in G1-phase when homologous recombination is unavailable. Complexes containing the Ku70/80 (“Ku”) and XRCC4/Ligase IV (Lig4) core C-NHEJ factors are required, respectively, for sensing joining DSBs. While absolutely required RAG1/2-endonucease (“RAG”)-initiated DSBs during V(D)J progenitor lymphocytes, cycling cells deficient also can join chromosomal by...