{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:10:23Z","timestamp":1791526223984,"version":"4.3.4"},"reference-count":82,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["IG 20528"],"award-info":[{"award-number":["IG 20528"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["14.Z50.31.0005"],"award-info":[{"award-number":["14.Z50.31.0005"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro","award":["FWGZ-2021-0017"],"award-info":[{"award-number":["FWGZ-2021-0017"]}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["IG 20528"],"award-info":[{"award-number":["IG 20528"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["14.Z50.31.0005"],"award-info":[{"award-number":["14.Z50.31.0005"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["FWGZ-2021-0017"],"award-info":[{"award-number":["FWGZ-2021-0017"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundamental Scientific Research Program of the Ministry of Education and Science of the Russian Federation","award":["IG 20528"],"award-info":[{"award-number":["IG 20528"]}]},{"name":"Fundamental Scientific Research Program of the Ministry of Education and Science of the Russian Federation","award":["14.Z50.31.0005"],"award-info":[{"award-number":["14.Z50.31.0005"]}]},{"name":"Fundamental Scientific Research Program of the Ministry of Education and Science of the Russian Federation","award":["FWGZ-2021-0017"],"award-info":[{"award-number":["FWGZ-2021-0017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The Drosophila abnormal spindle (asp) gene was discovered about 40 years ago and shown to be required for both mitotic and meiotic cell division. Subsequent studies showed that asp is highly conserved and that mutations in its human ortholog ASPM (Abnormal Spindle-like Microcephaly-associated; or MCPH5) are the most common cause of autosomal recessive primary microcephaly. This finding greatly stimulated research on ASPM and its fly and mouse (Aspm) orthologs. The three Asp orthologous proteins bind the microtubules (MTs) minus ends during cell division and also function in interphase nuclei. Investigations on different cell types showed that Asp\/Aspm\/ASPM depletion disrupts one or more of the following mitotic processes: aster formation, spindle pole focusing, centrosome-spindle coupling, spindle orientation, metaphase-to-anaphase progression, chromosome segregation, and cytokinesis. In addition, ASPM physically interacts with components of the DNA repair and replication machineries and is required for the maintenance of chromosomal DNA stability. We propose the working hypothesis that the asp\/Aspm\/ASPM genes play the same conserved functions in Drosophila, mouse, and human cells. Human microcephaly is a genetically heterogeneous disorder caused by mutations in 30 different genes that play a variety of functions required for cell division and chromosomal DNA integrity. Our hypothesis postulates that ASPM recapitulates the functions of most human microcephaly genes and provides a justification for why ASPM is the most frequently mutated gene in autosomal recessive primary microcephaly.<\/jats:p>","DOI":"10.3390\/cells12060922","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T04:10:48Z","timestamp":1679026248000},"page":"922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Multiple Mitotic Roles of the ASPM Orthologous Proteins: Insight into the Etiology of ASPM-Dependent Microcephaly"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-3660","authenticated-orcid":false,"given":"Alyona V.","family":"Razuvaeva","sequence":"first","affiliation":[{"name":"Department of Regulation of Genetic Processes, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia"},{"name":"Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Graziadio","sequence":"additional","affiliation":[{"name":"IBPM CNR c\/o Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-5039","authenticated-orcid":false,"given":"Gera A.","family":"Pavlova","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia V.","family":"Popova","sequence":"additional","affiliation":[{"name":"Department of Regulation of Genetic Processes, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia"},{"name":"Laboratory of Bioengineering, Novosibirsk State Agrarian University, Novosibirsk 630039, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6959-0641","authenticated-orcid":false,"given":"Alexey V.","family":"Pindyurin","sequence":"additional","affiliation":[{"name":"Department of Regulation of Genetic Processes, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bonaccorsi","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Patrizia","family":"Somma","sequence":"additional","affiliation":[{"name":"IBPM CNR c\/o Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3777-300X","authenticated-orcid":false,"given":"Maurizio","family":"Gatti","sequence":"additional","affiliation":[{"name":"IBPM CNR c\/o Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0092-8674(85)80071-4","article-title":"A cell division mutant of Drosophila with a functionally abnormal spindle","volume":"41","author":"Ripoll","year":"1985","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1083\/jcb.137.4.881","article-title":"The Drosophila gene abnormal spindle encodes a novel microtubule-associated protein that associates with the polar regions of the mitotic spindle","volume":"137","author":"Saunders","year":"1997","journal-title":"J. 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