2026-06-14T03:52:23Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/106732024-11-29T18:11:00Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Fundación La Caixa
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación Ramón Areces
funder
Unión Europea
funder
Comunidad de Madrid (España)
2020-07-06T16:34:35Z
2020-07-06T16:34:35Z
2015-01-26
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
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.
eng
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.
journal article
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