Paving the way for H2AX phosphorylation: chromatin changes in the DNA damage response.
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 HP1beta 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 HP1beta 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 HP1beta and the CK2 regulatory subunit. Interestingly, following its rapid mobilization, we find that HP1beta gradually re-accumulates on damaged chromatin over a longer time period, suggesting that temporal changes in HP1beta dynamics and interaction with chromatin may assist in different stages of the cellular response to DNA breakage.
The Medical Research Council Cancer Cell Unit, Cambridge, UK.
Nabieh
N
Ayoub
Anand D
AD
Jeyasekharan
Juan A
JA
Bernal
Ashok R
AR
Venkitaraman
D000818:Animals; D047390:Casein Kinase II / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D004249:DNA Damage / Q000235:genetics; D016678:Genome / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation
C000715593:CBX1 protein, human; D002843:Chromatin; D006657:Histones; D000090266:Chromobox Protein Homolog 5; D047390:Casein Kinase II