Phosphorylated KAP-1 fans out from DNA damage sites, spreading a message of chromatin relaxation, according to Yael Ziv, Yosef Shiloh (Tel Aviv University, Tel Aviv, Israel), and colleagues. The temporary relaxed state may allow proteins that detect and repair damage to gain better access to DNA.
Chromatin relaxation after DNA damage has been seen before but has been primarily a local effect at the site of damage. The Israeli group, however, documented a global effect that increased susceptibility to nuclease digestion throughout the genome.
The relaxation begins with the damage-detecting ATM kinase. The researchers found that ATM phosphorylates KAP-1, previously known as a transcription corepressor, and that this phosphorylated form spreads within minutes from the damage sites to a pan-nuclear localization. The result is a transient chromatin relaxation that lasts an hour or so. KAP-1 lacking the critical phosphorylation site does not induce relaxation.
The phosphorylated KAP-1 “is carrying a message to the chromatin,” says Shiloh. “If we had used 10 or 11 minutes as our first timepoint [it would have spread already and] we would have lost a critical element of this story.”
The group is now looking for proteins that interact with KAP-1 only before or only after phosphorylation, and for proteins or modifications that define the relaxed DNA state. The effect of that relaxed state is unknown; one possibility is that it helps the transcriptional apparatus to scan DNA for further damage.