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oai:repisalud.isciii.es:20.500.12105/106732024-11-29T18:11:00Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Trakala, Marianna author Rodríguez-Acebes, Sara author Maroto, María author Symonds, Catherine E author Santamaria, David author Malumbres, Marcos author Ortega Jimenez, Sagrario author Barbacid, Mariano author Mendez, Juan author Malumbres Martinez, Marcos author 2015-01-26 Polyploidization is a natural process that frequently accompanies differentiation; its deregulation is linked to genomic instability and cancer. Despite its relevance, why cells select different polyploidization mechanisms is unknown. Here we report a systematic genetic analysis of endomitosis, a process in which megakaryocytes become polyploid by entering mitosis but aborting anaphase. Whereas ablation of the APC/C cofactor Cdc20 results in mitotic arrest and severe thrombocytopenia, lack of the kinases Aurora-B, Cdk1, or Cdk2 does not affect megakaryocyte polyploidization or platelet levels. Ablation of Cdk1 forces a switch to endocycles without mitosis, whereas polyploidization in the absence of Cdk1 and Cdk2 occurs in the presence of aberrant re-replication events. Importantly, ablation of these kinases rescues the defects in Cdc20 null megakaryocytes. These findings suggest that endomitosis can be functionally replaced by alternative polyploidization mechanisms in vivo and provide the cellular basis for therapeutic approaches aimed to discriminate mitotic and polyploid cells. Dev Cell . 2015;32(2):155-67. 10.1016/j.devcel.2014.12.015 1878-1551 Developmental cell 25625205 http://hdl.handle.net/20.500.12105/10673 CYCLIN-DEPENDENT KINASES ENDOMITOTIC CELL-CYCLE S-PHASE RE-REPLICATION AURORA B GENE AMPLIFICATION; GENOMIC STABILITY MITOTIC EXIT; IN-VIVO; CDK1 Functional reprogramming of polyploidization in megakaryocytes.