Spatio-temporal dynamics of chromatin containing DNA breaks.
The cellular response to DNA breaks consists of a complex signaling network that coordinates the initial recognition of the lesion with the induction of cell cycle checkpoints and DNA repair. With DNA wrapped around histone proteins and packaged into higher order levels of chromatin structure, the detection of a single DNA break (DSB) in the genome is the molecular equivalent of finding a needle in a haystack. A recent study from our laboratory used high-resolution electron microscropy and live cell imaging to demonstrate that chromatin undergoes a marked reorganization in response to a DSB. In an energy dependent manner, chromatin rapidly decondenses to a more open configuration in the regions surrounding the lesion. We propose that this ATP dependent chromatin-remodeling event facilitates the subsequent recognition and processing of damaged DNA. While the chromatin surrounding the lesion remodels to a more open configuration, the DNA break itself remains relatively immobile over time, consistent with the idea that DNA damage response proteins migrate to positionally stable sites of damaged DNA. The lack of significant movement of chromatin regions containing DSBs has implications for the process by which chromosomal translocations form.
Kruhlak
Michael J
MJ
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1360, USA.
Celeste
Arkady
A
Nussenzweig
André
A
D000818:Animals; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage; D008957:Models, Genetic
D002843:Chromatin