Role of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DNA damage response

Ramos, Facundo; Villoria, María Teresa; Alonso-Rodríguez, Esmeralda; Clemente-Blanco, Andrés

Role of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DNA damage response

Authors:

Facundo Ramos¹, María Teresa Villoria¹, Esmeralda Alonso-Rodríguez¹ and Andrés Clemente-Blanco¹

Affiliations:

¹ Cell Cycle and Genome Stability Group. Institute of Functional Biology and Genomics (IBFG). Spanish National Research Council (CSIC), University of Salamanca (USAL), C/ Zacarías González 2, Salamanca 37007, SPAIN.

Keywords:

phosphatases, DNA damage response, PP1, PP2A, PP4, Cdc14.

Abbreviations:

CLL – chronic lymphocytic leukemia,

DDR – DNA damage response,

DSB – double strand break,

DUSP – dual-specificity phosphatase,

FEAR – fourteen early anaphase release,

HR – homologous recombination,

HU – hydroxyurea,

MEF – mouse embryonic fibroblasts,

MMS – methyl methanesulfonate

NHEJ – non-homologous endjoining,

NHL – non-Hodgkin lymphoma,

PPP – phosphoprotein phosphatase,

SAC – spindle assemble checkpoint,

SPB – spindle pole body, ss – single stranded.

Corresponding Author(s):

Andrés Clemente Blanco, Cell Cycle and Genome Stability Group. Institute of Functional Biology and Genomics (IBFG). Spanish National Research Council (CSIC), University of Salamanca (USAL), C/ Zacarías González 2, Salamanca 37007, SPAIN andresclemente@usal.es

Conflict of interest statement:

The authors declare no competing financial interests. Corre-spondence should be addressed to A.C-B.

Please cite this article as:

Facundo Ramos, María Teresa Villoria, Esmeralda Alonso-Rodríguez and Andrés Clemente-Blanco (2019). Role of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DNA damage response. Cell Stress 3(3): 70-85. doi: 10.15698/cst2019.03.178

© 2019 Ramos et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unre-stricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Maintenance of genome integrity is fundamental for cellular physiology. Our hereditary information encoded in the DNA is intrinsically susceptible to suffer variations, mostly due to the constant presence of endogenous and environmental genotoxic stresses. Genomic insults must be repaired to avoid loss or inappropriate transmission of the genetic information, a situation that could lead to the appearance of developmental anomalies and tumorigenesis. To safeguard our genome, cells have evolved a series of mechanisms collectively known as the DNA damage response (DDR). This surveillance system regulates multiple features of the cellular response, including the detection of the lesion, a transient cell cycle arrest and the restoration of the broken DNA molecule. While the role of multiple kinases in the DDR has been well documented over the last years, the intricate roles of protein dephosphorylation have only recently begun to be addressed. In this review, we have compiled recent information about the function of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DDR, focusing mainly on their capacity to regulate the DNA damage checkpoint and the repair mechanism encompassed in the restoration of a DNA lesion.