Early-onset Aging and Defective DNA Damage Response in Cdc14b-deficient Mice

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2011 Jan 26

PMID 21262768

Citations 24

Authors

Zhubo Wei

Sirisha Peddibhotla

Han Lin

Xiao Fang

Min Li

Jeffrey M Rosen

Pumin Zhang

Affiliations

Soon will be listed here.

Abstract

The Cdc14 dual-specificity phosphatase plays a key role in the mitotic exit of budding yeast cells. Mammals have two homologues, Cdc14a and Cdc14b. Unlike the yeast counterpart, neither Cdc14a nor Cdc14b seems to be essential for mitotic exit. To determine the physiological function of Cdc14b, we generated mice deficient in the phosphatase. The mutant mice were viable and did not display overt abnormalities. However, these mice developed signs of aging at much younger ages than the wild-type mice. At the cellular level, the Cdc14b-deficient mouse embryonic fibroblasts (MEFs) grew more slowly than the controls at later passages as a result of increased rates of senescence. Consistent with these premature-aging phenotypes, Cdc14b-deficient cells accumulated more endogenous DNA damage than the wild-type cells, and more Cdc14b-deficient MEFs entered senescence than control MEFs in response to exogenous DNA damage. However, no deficiencies in DNA damage checkpoint response were detected in Cdc14b mutant cells, suggesting that the function of Cdc14b is required for efficient DNA damage repair.

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