VRK1 chromatin kinase phosphorylates H2AX and is required for foci formation induced by DNA damage

Marcella Salzano, Marta Sanz-García, Diana M. Monsalve, David S. Moura, Pedro A. Lazo

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

All types of DNA damage cause a local alteration and relaxation of chromatin structure. Sensing and reacting to this initial chromatin alteration is a necessary trigger for any type of DNA damage response (DDR). In this context, chromatin kinases are likely candidates to participate in detection and reaction to a locally altered chromatin as a consequence of DNA damage and, thus, initiate the appropriate cellular response. In this work, we demonstrate that VRK1 is a nucleosomal chromatin kinase and that its depletion causes loss of histones H3 and H4 acetylation, which are required for chromatin relaxation, both in basal conditions and after DNA damage, independently of ATM. Moreover, VRK1 directly and stably interacts with histones H2AX and H3 in basal conditions. In response to DNA damage induced by ionizing radiation, histone H2AX is phosphorylated in Ser139 by VRK1. The phosphorylation of H2AX and the formation of gH2AX foci induced by ionizing radiation (IR), are prevented by VRK1 depletion and are rescued by kinase-active, but not kinase-dead, VRK1. In conclusion, we found that VRK1 is a novel chromatin component that reacts to its alterations and participates very early in DDR, functioning by itself or in cooperation with ATM.

Original languageEnglish (US)
Pages (from-to)373-383
Number of pages11
JournalEpigenetics
Volume10
Issue number5
DOIs
StatePublished - 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

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