Some repair proteins, such as 53BP1 (yellow, left), are broadly distributed along chromatin (red) surrounding lesions. Others, including RPA (yellow, right), accumulate specifically at the lesions.

A report on page 195 by Bekker-Jensen et al. maps out the damage-induced rearrangement of proteins involved in repairing double-stranded DNA breaks (DSBs). The map, the authors hope, will help scientists assign functions to future putative damage-responsive proteins.

Treatments such as ionizing radiation (and chemotherapy) that induce DSBs lead to the accumulation of nuclear foci containing repair proteins. Yet other proteins associated with the cellular response to DSBs do not join such foci.

The authors of the new report used lasers to induce DSBs on a scale that mimics environmental damage by radiation. They then classified known proteins involved in DSB repair according to their arrangement after the laser-induced damage. A protein's location, they discovered, was well-suited to its function.

Three kinds of foci were seen. One set was found on the single-stranded DNA that forms right at the break site. Proteins in these foci included those involved in the nitty gritty of damage repair via homologous recombination. Also included was ATR, which is an early-acting kinase that turns on the DNA damage checkpoint.

Another set of foci occupied a broader range, binding to chromatin as much as 1 Mb away from the lesion. Proteins in this set included adaptors that promote the interactions of checkpoint kinases (such as ATM) with their substrates or that simply concentrate repair proteins near the break site to increase repair efficiency.

A few proteins, including regulators that turn on and off the damage-sensing kinases, bridged these other two foci. Many proteins did not form foci at all. The authors believe that some of these are true messengers, which check in at the DNA, get activated at lesions, and then disseminate throughout the nucleus. These proteins include Chk1 and Chk2 kinases, which coordinate cell cycle progression, transcriptional changes, and replication fork stability in response to damage.

Checkpoint effectors such as Cdc25 and p53 never even approached the lesion but rather appeared merely to wait for messengers to reach them. They are thus already in position to stall DNA replication or alter transcription, as necessary.