Fragile when condensed

Tumor cells often have chromosomal breaks at conserved sequences known as fragile sites. Now, results from Eliane El Achkar, Michelle Debatisse (Institut Curie, Paris, France), and colleagues suggest that the chromatin can break if it condenses before these fragile sequences are fully replicated.

Fragile sites are especially sensitive to drugs that interfere with S phase. The group found that these same sites are also susceptible to a drug called calyculin A, which induces immediate chromatin condensation. DNA breaks appeared primarily when cells were treated with the drug during S phase or in G2. The further into G2 the drug was added, the fewer breaks were found, suggesting that whatever marks the sites as fragile was progressively corrected before mitosis.

The authors suspect that this “mark” is unreplicated DNA (or replicated DNA that has not...