Can I read USP1 deubiquitinase maintains phosphorylated CHK1 by limiting its DDB1-dependent degradation on EtoBox?

USP1 deubiquitinase maintains phosphorylated CHK1 by limiting its DDB1-dependent degradation by Jean-Hugues Guervilly; Emilie Renaud; Minoru Takata; Filippo Rosselli is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is USP1 deubiquitinase maintains phosphorylated CHK1 by limiting its DDB1-dependent degradation about?

The maintenance of genetic stability depends on the fine-tuned initiation and termination of pathways involved in cell cycle checkpoints and DNA repair. Here, we describe a new pathway that regulates checkpoint kinase 1 (CHK1) activity, a key element controlling both checkpoints and DNA repair. We show that the ubiquitin-specific peptidase 1 (USP1) deubiquitinase participates in the maintenance of both total and phosphorylated levels of CHK1 in response to genotoxic stress. We establish that USP1 depletion stimulates the damage-specific DNA-binding protein 1-dependent degradation of phosphorylated CHK1 in both a monoubiquitinylated Fanconi anaemia, complementation group D2 (FANCD2)-dependent and -independent manner. Our data support the existence of a circuit in which CHK1 activates checkpoints, DNA repair and proliferating cell nuclear antigen and FANCD2 monoubiquitinylation. The latter two events, in turn, switch off activated CHK1 by negative feedback inhibition, which contributes to the downregulation of the DNA damage response. This pathway, which is compromised in the cancer-prone disease Fanconi anaemia (FA), likely contributes to the hypersensitivity of cells from FA patien

Who reads USP1 deubiquitinase maintains phosphorylated CHK1 by limiting its DDB1-dependent degradation?

Author

Jean-Hugues Guervilly; Emilie Renaud; Minoru Takata; Filippo Rosselli

Publisher

Oxford University Press (OUP)

Published

2011

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)