4.6 Article

Paving the way for H2AX phosphorylation Chromatin changes in the DNA damage response

Journal

CELL CYCLE
Volume 8, Issue 10, Pages 1494-1500

Publisher

TAYLOR & FRANCIS INC
DOI: 10.4161/cc.8.10.8501

Keywords

heterochromatin; euchromatin; HP1 beta; casein kinase 2 (CK2); DNA damage; H2AX phosphorylation; FRAP; FLIP; 2D gels

Categories

Funding

  1. Medical Research Council
  2. Wellcome Trust
  3. Gates Foundation
  4. MRC [G0700651, G0600332, MC_U105359877, G9900064] Funding Source: UKRI
  5. Medical Research Council [G9900064, G0700651, MC_U105359877, G0600332] Funding Source: researchfish

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The dynamics of chromatin-associated proteins control the accessibility of DNA to essential biological transactions like transcription, replication, recombination and repair. Here, we briefly outline what is known about the chromatin changes that occur during the cellular response to DNA breakage, focusing on our recent findings revealing that the chromatin factor HP1 beta is mobilized within seconds after DNA damage by an unrecognized signaling cascade mediated by casein kinase 2 (CK2) phosphorylation, paving the way for histone H2AX phosphorylation. We also show here that HP1 beta mobilization is neither associated with histone H3 modification on Ser10, an alteration proposed to assist in HP1 ejection from chromatin, nor with evidence of a physical interaction between HP1 beta and the CK2 regulatory subunit. Interestingly, following its rapid mobilization, we find that HP1 beta gradually re-accumulates on damaged chromatin over a longer time period, suggesting that temporal changes in HP1 beta dynamics and interaction with chromatin may assist in different stages of the cellular response to DNA breakage.

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