A5072406702- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Eosinophilic Disorders and Syndromes
- Chromosomal and Genetic Variations
- Cellular transport and secretion
- Pluripotent Stem Cells Research
- Photosynthetic Processes and Mechanisms
- Cell Image Analysis Techniques
- Genetic Neurodegenerative Diseases
- Cancer-related molecular mechanisms research
- Plant Molecular Biology Research
- Cytokine Signaling Pathways and Interactions
- Cancer, Hypoxia, and Metabolism
- DNA Repair Mechanisms
- MicroRNA in disease regulation
- Cell death mechanisms and regulation
- Adipose Tissue and Metabolism
- Chronic Myeloid Leukemia Treatments
IFOM
2023
University of Milan
2021-2022
Istituto Nazionale Genetica Molecolare
2021-2022
University of Copenhagen
2011-2016
Novo Nordisk Foundation
2013-2016
Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
2006-2008
BubR1 is a central component of the spindle assembly checkpoint that inhibits progression into anaphase in response to improper kinetochore-microtubule interactions. In addition, also helps stabilize interactions by counteracting Aurora B kinase but mechanism behind this not clear. Here we show directly binds B56 family protein phosphatase 2A (PP2A) regulatory subunits through conserved motif phosphorylated cyclin-dependent 1 (Cdk1) and polo-like (Plk1). Two highly hydrophobic residues...
The Bub1-Bub3 and BubR1-Bub3 checkpoint complexes, or the Bubs, contribute to accurate segregation of chromosomes during mitosis by promoting chromosome bi-orientation halting exit from if this fails. complexes associate with kinetochores mitosis, which is required for proper segregation. outer kinetochore protein KNL1 (also known as CASC5/Blinkin/AF15Q14) receptor Bub proteins but exact nature functional binding sites on are yet be determined. Here, we show that contains multiple proteins,...
Abstract The spindle assembly checkpoint (SAC) ensures proper chromosome segregation by delaying anaphase onset in response to unattached kinetochores. Checkpoint signalling requires the kinetochore localization of Mad1–Mad2 complex that more eukaryotes depends on Rod–Zwilch–ZW10 (RZZ) complex. protein Zwint has been proposed be receptor for RZZ, but here we show Bub1 and not is required RZZ recruitment. We find middle region encompassing a domain essential SAC contributes localization. In...
Deciphering how the human striatum develops is necessary for understanding diseases that affect this region. To decode transcriptional modules regulate structure during development, we compiled a catalog of 1116 long intergenic noncoding RNAs (lincRNAs) identified de novo and then profiled 96,789 single cells from early fetal striatum. We found D1 D2 medium spiny neurons (D1- D2-MSNs) arise common progenitor lineage commitment established postmitotic transition, across pre-MSN phase exhibits...
The maintenance of genomic stability relies on the spindle assembly checkpoint (SAC), which ensures accurate chromosome segregation by delaying onset anaphase until all chromosomes are properly bioriented and attached to mitotic spindle. BUB1 BUBR1 kinases central for this process interacting with Blinkin, link SAC kinetochore, macromolecular that connects microtubules centromeric DNA. Here, we identify Blinkin motif critical interaction BUBR1, define stoichiometry affinity interaction,...
Huntington's disease is caused by a pathologically long (>35) CAG repeat located in the first exon of Huntingtin gene (HTT). While expanded repeats are focus extensive investigations, non-pathogenic tracts protein-coding genes less well characterized. Here, we investigated function and evolution physiological tract HTT gene. We show that poly-glutamine (polyQ) encoded CAGs huntingtin protein (HTT) under purifying selection subjected to stronger selective pressures than CAG-encoded polyQ...
Summary Ph‐negative chronic myeloproliferative disorders (CMPD) are characterized by constitutive Janus kinase‐signal transducer and activator of transcription (JAK‐STAT) activation. SOCS3 , SOCS1 PTPN6 ( SHP1 ) negative regulators the JAK‐STAT pathway. We investigated epigenetic genetic inactivation in 112 CMPD 20 acute myeloid leukaemia (AML) post‐CMPD. methylation occurred at high frequency both (46/112; 41·1%) AML post‐CMPD (10/17; 58·8%) was associated with transcriptional silencing. In...
Stem cell engineering of striatal medium spiny neurons (MSNs) is a promising strategy to understand diseases affecting the striatum and for cell-replacement therapies in different neurological diseases. Protocols generate cells from human pluripotent stem (PSCs) are scarce how well they recapitulate endogenous fetal remains poorly understood. We have developed protocol that modulates seeding density exposure specific morphogens generates authentic functional D1- D2-MSNs with high degree...
In vitro models of corticogenesis from pluripotent stem cells (PSCs) have greatly improved our understanding human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects in vivo cytoarchitecture the developing cortex. Here, we tested three protocols for regional identity, cell type specificity neuronal maturation. Overall, all gave rise organoids that displayed a time-dependent expression maturation genes such as those involved...
The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation during mitosis by delaying the activation of anaphase-promoting complex/cyclosome (APC/C) in response to unattached kinetochores. Mad2 protein is essential for a functional because it binds directly Cdc20, mitotic co-activator APC/C, thereby inhibiting progression into anaphase. exists at least 2 different conformations, open-Mad2 (O-Mad2) and closed-Mad2 (C-Mad2), with latter representing active form that able...
Drugs targeting microtubules rely on the mitotic checkpoint to arrest cell proliferation. The prolonged induced by such drugs is followed a G1 arrest. Here, we follow for several weeks fate of G1-arrested human cells after treatment with nocodazole. We find that small fraction escapes from and resumes These escaping experience reduced DNA damage p21 activation. Cells surviving are enriched anti-apoptotic proteins, including Triap1. Increasing Triap1 levels allows survive first lower p21;...
(Structure 19, 1691–1700; November 9, 2011) The original article unfortunately included two errors: one in the affiliations and figure correction. affiliation for David R. Spring was listed incorrectly, but appears correctly, above. Panel B Figure 3 printed without legend “Cdc16h-Cdc26 ribbon diagram representing protein Cdc16h.” revised panel is below. Structure of a Blinkin-BUBR1 Complex Reveals an Interaction Crucial Kinetochore-Mitotic Checkpoint Regulation via Unanticipated Binding...
ABSTRACT In vitro models of corticogenesis using mouse and human pluripotent stem cells (PSC) have greatly improved our understanding brain development disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects in vivo cytoarchitecture the developing cortex. Here, we tested three protocols for regional identity, cell type-specificity neuronal maturation. Overall all gave rise organoids that displayed a time-dependent expression maturation genes such as those...