A5065602633- Epigenetics and DNA Methylation
- Adenosine and Purinergic Signaling
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Pancreatic and Hepatic Oncology Research
- Biochemical and Molecular Research
- RNA Research and Splicing
- Nuclear Structure and Function
- Microtubule and mitosis dynamics
- Cancer Genomics and Diagnostics
- Multiple Myeloma Research and Treatments
- Cancer therapeutics and mechanisms
- RNA regulation and disease
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Protein Degradation and Inhibitors
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Bacterial Genetics and Biotechnology
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Adolescent and Pediatric Healthcare
- Plant Genetic and Mutation Studies
- Carcinogens and Genotoxicity Assessment
Institut de Génétique Humaine
2006-2024
Université de Montpellier
2020-2024
Centre National de la Recherche Scientifique
2008-2024
Centre de Recherche en Cancérologie de Toulouse
2019-2023
Heidelberg University
2002-2007
Nierenzentrum Heidelberg
2000
The Nup84p complex consists of five nucleoporins (Nup84p, Nup85p, Nup120p, Nup145p-C, and Seh1p) Sec13p, a bona fide subunit the COPII coat complex. We show that pool green fluorescent protein–tagged Sec13p localizes to nuclear pores in vivo, identify sec13 mutant alleles are synthetically lethal with nup85Δ affect localization protein–Nup49p reporter protein. In electron microscope, mutants exhibit structural defects pore (NPC) envelope organization. For assembly complex, Nup145p-C...
Abstract Cytidine deaminase (CDA) functions in the pyrimidine salvage pathway for DNA and RNA syntheses has been shown to protect cancer cells from deoxycytidine-based chemotherapies. In this study, we observed that CDA was overexpressed pancreatic adenocarcinoma patients at baseline essential experimental tumor growth. Mechanistic investigations revealed localized replication forks where it increased speed, improved fork restart efficiency, reduced endogenous stress, minimized breaks,...
The nuclear pore complex (NPC) gates the only known conduit for molecular exchange between nucleus and cytoplasm of eukaryotic cells. Macromolecular transport across NPC is mediated by nucleocytoplasmic shuttling receptors termed karyopherins (Kaps). Kaps interact with proteins (nucleoporins) that contain FG peptide repeats (FG Nups) altogether carry hundreds different cargoes NPC. Previously we described a biochemical strategy to identify individual components machinery. We used bacterially...
Hematopoiesis is particularly sensitive to DNA damage. Myeloid tumor incidence increases in patients with repair defects and after chemotherapy. It not known why hematopoietic cells are highly vulnerable Addressing this question complicated by the paucity of mouse models malignancies due defective repair. We show that repair-deficient Mcm8- Mcm9-knockout mice develop myeloid tumors, phenocopying prevalent myelodysplastic syndromes. demonstrate these tumors preceded a lifelong damage burden...
About 30 different nucleoporins (Nups) constitute the nuclear pore complex. We have affinity-purified 28 of these proteins and identified new nucleoporin interactions by this analysis. found that Nup157 Nup170, two members large structural Nups, Gly-Leu-Phe-Gly Nup145N specifically co-purified with Nup84 In addition, co-enriched during purification. By in vitro reconstitution, we demonstrate form a subcomplex. Moreover, show bind to heptameric This assembly thus represents approximately...
Multiple myeloma (MM) is a hematological malignancy characterized by an abnormal clonal proliferation of malignant plasma cells. Despite the introduction novel agents that have significantly improved clinical outcome, most patients relapse and develop drug resistance. MM genomic instability high level replicative stress. In response to DNA damage stress, cells activate various signaling pathways. this study, we reported CHK1 WEE1 expression associated with poor outcome in independent cohorts...
Abstract The exonuclease domain of DNA polymerases epsilon's catalytic subunit (POLE) removes misincorporated nucleotides, called proofreading. POLE-exonuclease mutations cause colorectal- and endometrial cancers with an extreme burden single nucleotide substitutions. We recently reported that particularly the hereditary POLE mutation N363K predisposes in addition to aggressive giant cell glioblastomas. knocked-in this homozygously into human lines compared its properties knock-ins likewise...
In all eukaryotes, the heterohexameric MCM2-7 complex functions as main replicative helicase during S phase. During early G1 phase, it is recruited onto chromatin in a sequence of reactions called pre-replication (pre-RC) formation or DNA licensing. This process ATP-dependent and at least two different chromatin-bound ATPase activities are required besides several others essential, but not enzymatically active, proteins. Although functionally conserved evolution, pre-RC way loaded more...
SUMMARY DNA replication initiates with pre-replication complex (pre-RC) formation at origins in G1 (replication origin licensing), followed by activation of a pre-RC subset the S phase. It has been suggested that checkpoint prevents phase entry when too few are licensed. Yet, we found normal cells, complete synthesis inhibition overexpression non-degradable geminin variant, or CDT1 silencing without inducing any checkpoint. Cells continue cycling and enter mitosis, despite absence replicated...
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