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Cell Mol Life Sci. 2018 Jul;75(13):2375-2388. doi: 10.1007/s00018-018-2811-2. Epub 2018 Apr 20.

Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?

Author information

1
Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, 37007, Salamanca, Spain.
2
Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, 37007, Salamanca, Spain.
3
Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, 37007, Salamanca, Spain. pedro.lazo@csic.es.
4
Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, 37007, Salamanca, Spain. pedro.lazo@csic.es.

Abstract

DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). This initiating kinase must be located in chromatin, and be activated independently of the type of DNA damage. We review the contribution of the Ser-Thr vaccinia-related kinase 1 (VRK1) chromatin kinase as a new player in the signaling of DNA damage responses, at chromatin and cellular levels, and its potential as a new therapeutic target in oncology. VRK1 is involved in the regulation of histone modifications, such as histone phosphorylation and acetylation, and in the formation of γH2AX, NBS1 and 53BP1 foci induced in DDR. Induction of DNA damage by chemotherapy or radiation is a mainstay of cancer treatment. Therefore, novel treatments can be targeted to proteins implicated in the regulation of DDR, rather than by directly causing DNA damage.

KEYWORDS:

53BP1; DNA damage response; H2AX; Ionizing radiation; NBS1; Phosphorylation; VRK1; p53

PMID:
29679095
PMCID:
PMC5986855
DOI:
10.1007/s00018-018-2811-2
[Indexed for MEDLINE]
Free PMC Article

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