CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Marko Marjanovic
- Carlos Sanchez-Huertas
- Berta Terre
- Rocio Gomez
- Jan Frederik Scheel
- Sarai Pacheco
- Philip A Knobel
- Ana Martinez-Marchal
- Suvi Aivio
- Lluis Palenzuela
- Uwe Wolfrum
- Peter J McKinnon
- Jose A Suja
- Ignasi Roig
- Vincenzo Costanzo
- Jens Lueders
- Travis H Stracker
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000358858100020&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1038/ncomms8676
- Externe Identifier
- Clarivate Analytics Document Solution ID: CO0QW
- PubMed Identifier: 26158450
- ISSN
- 2041-1723
- Zeitschrift
- NATURE COMMUNICATIONS
- Artikelnummer
- ARTN 7676
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Titel
- CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination
- Sub types
- Article
- Ausgabe der Zeitschrift
- 6
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Marko Marjanović
- Carlos Sánchez-Huertas
- Berta Terré
- Rocío Gómez
- Jan Frederik Scheel
- Sarai Pacheco
- Philip A Knobel
- Ana Martínez-Marchal
- Suvi Aivio
- Lluís Palenzuela
- Uwe Wolfrum
- Peter J McKinnon
- José A Suja
- Ignasi Roig
- Vincenzo Costanzo
- Jens Lüders
- Travis H Stracker
- DOI
- 10.1038/ncomms8676
- eISSN
- 2041-1723
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Nature Communications
- Sprache
- en
- Artikelnummer
- 7676
- Online publication date
- 2015
- Status
- Published online
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1038/ncomms8676
- Datum der Datenerfassung
- 2023
- Titel
- CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination
- Ausgabe der Zeitschrift
- 6
Datenquelle: Crossref
- Abstract
- CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63-deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death, and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63-deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination.
- Addresses
- 1] Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain [2] Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb 10000, Croatia.
- Autoren
- Marko Marjanović
- Carlos Sánchez-Huertas
- Berta Terré
- Rocío Gómez
- Jan Frederik Scheel
- Sarai Pacheco
- Philip A Knobel
- Ana Martínez-Marchal
- Suvi Aivio
- Lluís Palenzuela
- Uwe Wolfrum
- Peter J McKinnon
- José A Suja
- Ignasi Roig
- Vincenzo Costanzo
- Jens Lüders
- Travis H Stracker
- DOI
- 10.1038/ncomms8676
- eISSN
- 2041-1723
- Externe Identifier
- PubMed Identifier: 26158450
- PubMed Central ID: PMC4499871
- Funding acknowledgements
- Telethon: GGP13071
- NINDS NIH HHS: R56 NS037956
- NINDS NIH HHS: NS-37956
- NINDS NIH HHS: R01 NS037956
- European Research Council: 614541
- NCI NIH HHS: P30 CA-21765
- NCI NIH HHS: P01 CA096832
- NCI NIH HHS: CA-21765
- NCI NIH HHS: P30 CA021765
- Worldwide Cancer Research: 13-0026
- Open access
- true
- ISSN
- 2041-1723
- Zeitschrift
- Nature communications
- Schlüsselwörter
- Spermatocytes
- Centrosome
- Animals
- Mice
- Dwarfism
- Microcephaly
- DNA Damage
- Facies
- Cell Cycle Proteins
- Sperm Count
- Immunohistochemistry
- Meiosis
- Recombination, Genetic
- Male
- Tumor Suppressor Protein p53
- Real-Time Polymerase Chain Reaction
- Homologous Recombination
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2015
- Open access status
- Open Access
- Paginierung
- 7676
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum der Datenerfassung
- 2015
- Titel
- CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Research Support, N.I.H., Extramural
- Ausgabe der Zeitschrift
- 6
Files
https://www.nature.com/articles/ncomms8676.pdf https://europepmc.org/articles/PMC4499871?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63-deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death, and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63-deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination.
- Date of acceptance
- 2015
- Autoren
- Marko Marjanović
- Carlos Sánchez-Huertas
- Berta Terré
- Rocío Gómez
- Jan Frederik Scheel
- Sarai Pacheco
- Philip A Knobel
- Ana Martínez-Marchal
- Suvi Aivio
- Lluís Palenzuela
- Uwe Wolfrum
- Peter J McKinnon
- José A Suja
- Ignasi Roig
- Vincenzo Costanzo
- Jens Lüders
- Travis H Stracker
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/26158450
- DOI
- 10.1038/ncomms8676
- eISSN
- 2041-1723
- Externe Identifier
- NIH Manuscript Submission ID: NIHMS696224
- PubMed Central ID: PMC4499871
- Funding acknowledgements
- NINDS NIH HHS: R56 NS037956
- Telethon: GGP13071
- NINDS NIH HHS: R01 NS037956
- NINDS NIH HHS: NS-37956
- European Research Council: 614541
- NCI NIH HHS: P30 CA-21765
- NCI NIH HHS: CA-21765
- NCI NIH HHS: P30 CA021765
- NCI NIH HHS: P01 CA096832
- Zeitschrift
- Nat Commun
- Schlüsselwörter
- Animals
- Cell Cycle Proteins
- Centrosome
- DNA Damage
- Dwarfism
- Facies
- Homologous Recombination
- Immunohistochemistry
- Male
- Meiosis
- Mice
- Microcephaly
- Real-Time Polymerase Chain Reaction
- Recombination, Genetic
- Sperm Count
- Spermatocytes
- Tumor Suppressor Protein p53
- Sprache
- eng
- Country
- England
- Paginierung
- 7676
- PII
- ncomms8676
- Datum der Veröffentlichung
- 2015
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2016
- Titel
- CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination.
- Sub types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 6
Datenquelle: PubMed
- Beziehungen:
- Eigentum von