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. 2010 Sep 22:8:27.
doi: 10.1186/1478-811X-8-27.

Phosphatases in the cellular response to DNA damage

Alyson K Freeman  1 , Alvaro Na Monteiro
Affiliations

Phosphatases in the cellular response to DNA damage

Alyson K Freeman et al. Cell Commun Signal. .

Abstract

In the last fifteen years, rapid progress has been made in delineating the cellular response to DNA damage. The DNA damage response network is composed of a large number of proteins with different functions that detect and signal the presence of DNA damage in order to coordinate DNA repair with a variety of cellular processes, notably cell cycle progression. This signal, which radiates from the chromatin template, is driven primarily by phosphorylation events, mainly on serine and threonine residues. While we have accumulated detailed information about kinases and their substrates our understanding of the role of phosphatases in the DNA damage response is still preliminary. Identifying the phosphatases and their regulation will be instrumental to obtain a complete picture of the dynamics of the DNA damage response. Here we give an overview of the DNA damage response in mammalian cells and then review the data on the role of different phosphatases and discuss their biological relevance.

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Figures

Figure 1
Figure 1
A simplified view of the cellular response to DNA damage. Single and double stranded DNA breaks signal through the sensors (MRN and 9-1-1) shown in purple, mediators (H2AX, BRCA1, MDC1, 53BP1) shown in blue, signal transducing kinases (ATM, ATR) shown in yellow, effector kinases (CHK2, CHK1) shown in pink, and effector proteins (E2F1, p53, Cdc25) shown in green, leading to gene transcription, apoptosis, and cell cycle arrest. Proteins that are phosphorylated by ATM, ATR, and/or DNA-PK are marked by a yellow phosphate group and proteins that are phosphorylated by CHK2 and/or CHK1 are marked by a pink phosphate group.
Figure 2
Figure 2
Protein serine/threonine phosphatases in the DNA damage response pathway. The positive (arrows) and negative regulation of DDR proteins via protein serine/threonine phosphatases is shown.
See this image and copyright information in PMC

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