Andrea Musacchio

Summary

Country: Italy

Publications

  1. ncbi The spindle-assembly checkpoint in space and time
    Andrea Musacchio
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Nat Rev Mol Cell Biol 8:379-93. 2007
  2. pmc Determinants of conformational dimerization of Mad2 and its inhibition by p31comet
    Marina Mapelli
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    EMBO J 25:1273-84. 2006
  3. ncbi Architecture of the human ndc80-hec1 complex, a critical constituent of the outer kinetochore
    Claudio Ciferri
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    J Biol Chem 280:29088-95. 2005
  4. pmc Structural analysis reveals features of the spindle checkpoint kinase Bub1-kinetochore subunit Knl1 interaction
    Veronica Krenn
    Department of Experimental Oncology, European Institute of Oncology, 20139 Milan, Italy
    J Cell Biol 196:451-67. 2012
  5. ncbi The Mad2 conformational dimer: structure and implications for the spindle assembly checkpoint
    Marina Mapelli
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, I 20139, Milan, Italy
    Cell 131:730-43. 2007
  6. pmc A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B
    Anna De Antoni
    Department of Experimental Oncology, European Institute of Oncology, 20139 Milan, Italy
    J Cell Biol 199:269-84. 2012
  7. ncbi The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint
    Anna De Antoni
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy
    Curr Biol 15:214-25. 2005
  8. pmc The influence of catalysis on mad2 activation dynamics
    Marco Simonetta
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    PLoS Biol 7:e10. 2009
  9. pmc The MIS12 complex is a protein interaction hub for outer kinetochore assembly
    Arsen Petrovic
    Department of Experimental Oncology, European Institute of Oncology IEO, Milan, Italy
    J Cell Biol 190:835-52. 2010
  10. pmc Accumulation of Mad2-Cdc20 complex during spindle checkpoint activation requires binding of open and closed conformers of Mad2 in Saccharomyces cerevisiae
    Luigi Nezi
    Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy
    J Cell Biol 174:39-51. 2006

Collaborators

Detail Information

Publications41

  1. ncbi The spindle-assembly checkpoint in space and time
    Andrea Musacchio
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Nat Rev Mol Cell Biol 8:379-93. 2007
    ..These studies are finally starting to reveal the mechanisms of checkpoint activation and silencing during mitotic progression...
  2. pmc Determinants of conformational dimerization of Mad2 and its inhibition by p31comet
    Marina Mapelli
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    EMBO J 25:1273-84. 2006
    ..We also show that the negative effects of p31comet on the SAC are based on its competition with O-Mad2 for C-Mad2 binding...
  3. ncbi Architecture of the human ndc80-hec1 complex, a critical constituent of the outer kinetochore
    Claudio Ciferri
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    J Biol Chem 280:29088-95. 2005
    ..The recombinant complex displays normal kinetochore localization upon injection in HeLa cells and is therefore a faithful copy of the endogenous Ndc80 complex...
  4. pmc Structural analysis reveals features of the spindle checkpoint kinase Bub1-kinetochore subunit Knl1 interaction
    Veronica Krenn
    Department of Experimental Oncology, European Institute of Oncology, 20139 Milan, Italy
    J Cell Biol 196:451-67. 2012
    ..These results shed light on the determinants of kinetochore recruitment of Bub1...
  5. ncbi The Mad2 conformational dimer: structure and implications for the spindle assembly checkpoint
    Marina Mapelli
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, I 20139, Milan, Italy
    Cell 131:730-43. 2007
    ..The structure of the O-Mad2-C-Mad2 conformational dimer is consistent with a catalytic model in which a C-Mad2 template facilitates the binding of O-Mad2 to Cdc20, the target of Mad2 in the spindle checkpoint...
  6. pmc A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B
    Anna De Antoni
    Department of Experimental Oncology, European Institute of Oncology, 20139 Milan, Italy
    J Cell Biol 199:269-84. 2012
    ..This result suggests that a target of 5-ITu, possibly Haspin itself, may further contribute to SAC signaling downstream of Aurora B...
  7. ncbi The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint
    Anna De Antoni
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy
    Curr Biol 15:214-25. 2005
    ..These events are linked to the existence of two distinct conformers of Mad2: a closed conformer bound to its kinetochore receptor Mad1 or its target in the checkpoint Cdc20 and an open conformer unbound to these ligands...
  8. pmc The influence of catalysis on mad2 activation dynamics
    Marco Simonetta
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    PLoS Biol 7:e10. 2009
    ..e., it is purely catalytic. These results surpass previously formulated objections to the Mad2-template model and predict that the release of Mad2 from Cdc20 is an energy-driven process...
  9. pmc The MIS12 complex is a protein interaction hub for outer kinetochore assembly
    Arsen Petrovic
    Department of Experimental Oncology, European Institute of Oncology IEO, Milan, Italy
    J Cell Biol 190:835-52. 2010
    ..Our analysis has important implications for understanding kinetochore organization in different organisms...
  10. pmc Accumulation of Mad2-Cdc20 complex during spindle checkpoint activation requires binding of open and closed conformers of Mad2 in Saccharomyces cerevisiae
    Luigi Nezi
    Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy
    J Cell Biol 174:39-51. 2006
    ..Our biochemical and genetic evidence shows that the interaction of O- and C-Mad2 is essential for the SAC and is conserved in evolution...
  11. ncbi In vitro FRAP identifies the minimal requirements for Mad2 kinetochore dynamics
    Martin Vink
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Curr Biol 16:755-66. 2006
    ..Whether specifically this interaction accounts for the kinetochore dynamics of Mad2 is currently unknown...
  12. pmc Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction
    Stefano Santaguida
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    EMBO J 30:1508-19. 2011
    ..Our results support a model in which Aurora B is at the apex of a signalling pyramid whose sensory apparatus promotes the concomitant activation of error correction and checkpoint signalling pathways...
  13. doi Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex
    Claudio Ciferri
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, I 20139 Milan, Italy
    Cell 133:427-39. 2008
    ..We discuss our results with reference to current models of kinetochore-microtubule attachment and centromere organization...
  14. pmc Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine
    Stefano Santaguida
    Department of Experimental Oncology, European Institute of Oncology, I 20139 Milan, Italy
    J Cell Biol 190:73-87. 2010
    ..They also shed light on the relationship between the error correction pathway and the spindle checkpoint and suggest that these processes are coregulated and are likely to share at least a subset of their catalytic machinery...
  15. pmc A screen for kinetochore-microtubule interaction inhibitors identifies novel antitubulin compounds
    Emanuela Screpanti
    Department of Experimental Oncology, European Institute of Oncology, IFOM IEO Campus, Milan, Italy
    PLoS ONE 5:e11603. 2010
    ..We set out to identify small compounds that inhibit kinetochore-microtubule binding for use in kinetochore-spindle interaction studies and to develop them into novel anticancer drugs...
  16. ncbi Mechanism of Aurora B activation by INCENP and inhibition by hesperadin
    Fabio Sessa
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Mol Cell 18:379-91. 2005
    ..Phosphorylation of two serines in the carboxyl terminus of INCENP generates the fully active kinase...
  17. pmc Direct binding of Cenp-C to the Mis12 complex joins the inner and outer kinetochore
    Emanuela Screpanti
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Curr Biol 21:391-8. 2011
    ..Our studies unveil a crucial and likely universal link between the inner and outer kinetochore...
  18. doi Sister chromatid tension and the spindle assembly checkpoint
    Luigi Nezi
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Curr Opin Cell Biol 21:785-95. 2009
    ..We discuss how tension-sensitive phenomena, such as attachment correction and stabilization, relate to the SAC and we speculate on the existence of a single pathway linking error correction and SAC activation...
  19. pmc Sgt1 is required for human kinetochore assembly
    Peter Steensgaard
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    EMBO Rep 5:626-31. 2004
    ..Our studies implicate Sgt1 as an essential protein and a critical assembly factor for the mammalian kinetochore, and lend credit to the hypothesis of a kinetochore assembly pathway that is conserved from yeast to man...
  20. ncbi The Ndc80 complex: hub of kinetochore activity
    Claudio Ciferri
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, I 20131 Milan, Italy
    FEBS Lett 581:2862-9. 2007
    ..Here, we describe how current work is contributing to unravel the complex endeavors of this essential kinetochore complex...
  21. pmc Explaining the oligomerization properties of the spindle assembly checkpoint protein Mad2
    Anna DeAntoni
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Philos Trans R Soc Lond B Biol Sci 360:637-47, discussion 447-8. 2005
    ..We discuss Mad2 oligomerization and link our discoveries to previous observations related to Mad2 oligomerization...
  22. pmc Spindly attachments
    Filiz Civril
    Department of Experimental Oncology, European Institute of Oncology, I 20139 Milan, Italy
    Genes Dev 22:2302-7. 2008
    ..2385-2399 present an analysis of the recently discovered Spindly/SPDL-1 protein that casts new lights onto the attachment process and the way it relates to the control of cell cycle progression...
  23. doi Homeostatic control of mitotic arrest
    Gianluca Varetti
    Department of Experimental Oncology, European Institute of Oncology Via Adamello 16, 20139 Milan, Italy
    Mol Cell 44:710-20. 2011
    ..Our studies reveal a homeostatic network in which checkpoint-sustaining and -repressing forces oppose each other during mitotic arrest and suggest ways for enhancing the sensitivity of cancer cells to antitubulin chemotherapeutics...
  24. pmc Spindle assembly checkpoint: the third decade
    Andrea Musacchio
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy
    Philos Trans R Soc Lond B Biol Sci 366:3595-604. 2011
    ..Here, we take a molecular view on the main challenges hampering this task...
  25. pmc The life and miracles of kinetochores
    Stefano Santaguida
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    EMBO J 28:2511-31. 2009
    ..In this review, we discuss how the molecular organization of the four modules allows a dynamic integration of kinetochore-microtubule attachment with the prevention of chromosome segregation errors and cell-cycle progression...
  26. doi The spindle assembly checkpoint
    Gianluca Varetti
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, I 20139 Milan, Italy
    Curr Biol 18:R591-5. 2008
  27. doi Structural analysis of the RZZ complex reveals common ancestry with multisubunit vesicle tethering machinery
    Filiz Civril
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, I 20139 Milan, Italy
    Structure 18:616-26. 2010
    ..The RZZ, limited to metazoans, probably evolved from the NRZ, exploiting the dynein-binding capacity of ZW10 to direct dynein to kinetochores...
  28. ncbi MAD contortions: conformational dimerization boosts spindle checkpoint signaling
    Marina Mapelli
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, I 20139 Milan, Italy
    Curr Opin Struct Biol 17:716-25. 2007
    ..These models add a molecular framework to an old theory that depicts kinetochores as catalysts in the generation of the mitotic checkpoint signal...
  29. doi A general framework for inhibitor resistance in protein kinases
    Deborah Balzano
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy
    Chem Biol 18:966-75. 2011
    ..Our results uncover a unifying mechanism of inhibitor resistance of protein kinases that might have widespread significance for drug target validation and clinical practice...
  30. ncbi Mechanism of CDK5/p25 binding by CDK inhibitors
    Marina Mapelli
    Structural Biology Unit, Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    J Med Chem 48:671-9. 2005
    ..The CDK5/p25 crystals represent a valuable new tool for the identification and optimization of selective CDK inhibitors...
  31. pmc Crystal structure of the catalytic domain of Haspin, an atypical kinase implicated in chromatin organization
    Fabrizio Villa
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy
    Proc Natl Acad Sci U S A 106:20204-9. 2009
    ..Overall, the structure of the Haspin kinase domain reveals an active conformation that is poised for substrate recognition and phosphorylation in the absence of external regulators...
  32. doi Cell cycle: deconstructing tension
    Andrea Musacchio
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, Milan, Italy
    Curr Biol 20:R634-7. 2010
    ..Removal of sister chromatid cohesion is predicted to cause a fall in tension. Two studies shed light on how cells avoid re-activation of the spindle checkpoint when cohesion is lost...
  33. ncbi The spindle checkpoint: structural insights into dynamic signalling
    Andrea Musacchio
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Nat Rev Mol Cell Biol 3:731-41. 2002
    ..Here, we review and integrate findings on the dynamics of checkpoint proteins at kinetochores with structural information about signalling complexes...
  34. doi KI motifs of human Knl1 enhance assembly of comprehensive spindle checkpoint complexes around MELT repeats
    Veronica Krenn
    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto Hahn Strasse 11, 44227 Dortmund, Germany Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy
    Curr Biol 24:29-39. 2014
    ..Met-Glu-Leu-Thr (MELT) repeats, ubiquitous in evolution, recruit the Bub3/Bub1 complex in a phosphorylation-dependent manner. The exact contributions of KI and MELT motifs to SAC signaling and chromosome alignment are unclear...
  35. ncbi Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase
    Cataldo Tarricone
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Neuron 44:809-21. 2004
    ..Our data suggest that the LIS1 molecule undergoes major conformational rearrangement when switching from a complex with the acetylhydrolase to the one with Ndel1...
  36. pmc Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a 'safety belt' binding mechanism for the spindle checkpoint
    Lucia Sironi
    Structural Biology Unit, Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    EMBO J 21:2496-506. 2002
    ..We also show that unlocking the Mad2 C-terminal tail is required for ligand release from Mad2, and that the 'safety belt' mechanism may prolong the lifetime of Mad2-ligand complexes...
  37. ncbi Kinetochore microtubule dynamics and attachment stability are regulated by Hec1
    Jennifer G DeLuca
    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cell 127:969-82. 2006
    ..These findings reveal a key role for the Hec1 N terminus in controlling dynamic behavior of kinetochore microtubules...
  38. ncbi Molecular basis for the specificity of p27 toward cyclin-dependent kinases that regulate cell division
    Eilyn R Lacy
    Department of Structural Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    J Mol Biol 349:764-73. 2005
    ....
  39. ncbi Molecular basis of drug resistance in aurora kinases
    Fiona Girdler
    Faculty of Life Sciences, University of Manchester, Manchester, UK
    Chem Biol 15:552-62. 2008
    ..Furthermore, because the plasticity of the ATP-binding pocket renders Aurora B insensitive to multiple inhibitors, our observations indicate that the drug-resistant Aurora B mutants should be exploited as novel drug targets...
  40. ncbi PLK1 inhibitors: setting the mitotic death trap
    Simon Plyte
    Congenia S r l, Genextra Group, Via Adamello 16, I 20139 Milan, Italy
    Curr Biol 17:R280-3. 2007
    ..Analysis of the cytological and anti-tumor activities of BI 2536, a novel, selective pharmacological inhibitor of Plk1, has connected chemistry and biology to the bedside...
  41. pmc Comment on "A centrosome-independent role for gamma-TuRC proteins in the spindle assembly checkpoint"
    Stephen S Taylor
    Faculty of Life Sciences, University of Manchester, Manchester, UK
    Science 316:982; author reply 982. 2007
    ..Because gamma-TuRC inhibition leads to pleiotropic spindle defects, which are well known to activate kinetochore-derived checkpoint signaling, we believe that this conclusion is premature...