Uncoupling of S phase and mitosis in cardiomyocytes and hepatocytes lacking the winged-helix transcription factor Trident

Wouter Korver, Marco W. Schilham, Petra Moerer, Maurice J. Van Den Hoff, Klaas Dam, Wouter H. Lamers, René H. Medema, Hans Clevers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

116 Citaten (Scopus)

Samenvatting

In order to maintain a stable karyotype, the eukaryotic cell cycle is coordinated such that only one round of S phase precedes each mitosis, and mitosis is not initiated until DNA replication is completed. Several checkpoints and regulatory proteins have been defined in lower eukaryotes that govern this coordination, but little is known about the proteins that are involved in mammalian cells. Previously, we have shown that the winged-helix transcription factor Trident - also known as HFH-11, FKL16 and WIN-is exclusively expressed in cycling cells and is phosphorylated during mitosis. The cellular function of Trident has yet to be described, however. Here, we have shown that disruption of the Trident gene in mice resulted in postnatal death, most probably because of circulatory failure. Histological analysis of Trident(-/-) embryos from embryonic day 10 (E10) onwards revealed a specific, characteristic defect in the developing myocardium. The orientation of the myocytes was highly irregular and the nuclei of these disorganized cardiomyocytes were clearly polyploid with up to a 50-fold increase in DNA content. Polyploidy was also observed in embryonic hepatocytes. Our results indicate that expression of Trident is required to prevent multiple rounds of S phase in the heart and the liver. Trident therefore appears to have a role in preventing DNA re-replication during the G2 and M phases.

Originele taal-2Engels
Pagina's (van-tot)1327-1330
Aantal pagina's4
TijdschriftCurrent Biology
Volume8
Nummer van het tijdschrift24
DOI's
StatusGepubliceerd - 3 dec. 1998
Extern gepubliceerdJa

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