Introduction
In the letter by Mailand et al. (Nature Cell Biol. 4, 317–322; 2002), we showed that conditional overexpression of the phosphatase Cdc14A results in premature centrosome splitting, supernumerary mitotic spindles and aberrant chromosomal partitioning. During ensuing work, we found that the supposedly wild-type Cdc14A transgene integrated in our model cell line had a point mutation (C278S) in the phosphatase domain. To clarify whether the described deregulation of the centrosome cycle requires the catalytic activity of Cdc14A, we generated a new panel of cell lines (derived from the same parental U2-OS cells as in the original study) conditionally expressing bona fide wild-type (WT) or phosphatase-dead (PD; C278S) Cdc14A alleles. We verified the transgenes by sequencing and re-analysed the phenotypes described in the original paper. The results confirmed our previous findings by showing that the excess of Cdc14A induces premature centrosome splitting and formation of supernumerary mitotic spindles. Importantly, however, analysis of multiple independent clones conditionally expressing either Cdc14A-WT or Cdc14A-PD, revealed a similar spectrum and incidence of these phenotypes.
Therefore, we have to correct our previous conclusion that overexpression of catalytically inactive Cdc14A has no phenotype — the lack of obvious centrosomal defects in the Cdc14A-PD cell line reported in the original paper is, in fact, atypical and may be due to the slower induction of the transgene expression in this clone. Based on the data obtained with the new cell lines, we conclude that premature centrosome splitting and malfunction of the mitotic spindle induced by overexpressed Cdc14A does not require its catalytic function. Rather, these abnormalities reflect changes in stoichiometry of Cdc14A interactions with other proteins and the imbalance of these interactions at the centrosome. It is noteworthy that Cdc14A overproduction causes a G2 delay in all Cdc14A-WT-, but not Cdc14A-PD-cell lines. Thus, regulation of mitotic entry may be a catalytic function of mammalian Cdc14A.
We apologize for the mistake in our original paper and we will provide the new inducible cell lines on request and share the details of their characterization. A separate study published by two of us (Kaiser , B. & Jackson , P.Mol. Biol. Cell, 13, 2289–2300; 2002) also showed that overexpression of Cdc14A caused disruption of the centrosome and malfunction of the mitotic spindle. The Cdc14A construct in this study was verified as wild type, as originally reported.
