Mobilization and recruitment of HP1: a bimodal response to DNA breakage.

摘要: The pathways that signal double-strand DNA breaks (DSBs) in mammalian cells are central to the maintenance of genome integrity. We have reported (Ayoub et al., Nature 2008; 453: 682-6) rapid mobilization heterochromatin protein, HP1beta, within seconds from DSB sites promotes chromatin changes like H2AX phosphorylation trigger this response. Notably, paper and a subsequent report Cell Cycle 2009; 8: 1494-500), demonstrate transient HP1beta is followed by its accumulation over time at sites. Indeed, two recent papers (Luijsterburg J Biol 185:577-86 Zarebski Cytometry A May 2009) suggest HP1 recruitment damage sites, rather than mobilization, predominant behaviour exhibited protein. Here, we present new experimental analyses which corroborate fluorophore-tagged exhibits distinct behaviours living - rapid, most evident heterochromatic regions, slower recruitment. Experimental methods allowing visualization these described. Interestingly, chemical inhibition DNA-damage responsive enzyme, casein kinase 2 (CK2), suppresses while permitting Our findings reconcile model, wherein DSBs mediated on Thr51 CK2, by, may overlap with, via chromoshadow domain, independent Thr51. provide fresh insight into earliest events response cells.