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Título

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

AutorCampillo-Marcos, Ignacio ; Lazo, Pedro A.
Palabras claveNBS1
p53
VRK1
Phosphorylation
Ionizing radiation
H2AX
DNA damage response
53BP1
Fecha de publicación2018
EditorSpringer Nature
CitaciónCellular and Molecular Life Sciences 75(13): 2375-2388 (2018)
ResumenDNA 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 ¿H2AX, 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.
Versión del editorhttps://doi.org/10.1007/s00018-018-2811-2
URIhttp://hdl.handle.net/10261/168053
Identificadoresdoi: 10.1007/s00018-018-2811-2
issn: 1420-682X
e-issn: 1420-9071
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