A cytoplasmic enzyme called N4BP2 has been identified as a key driver of catastrophic chromosome shattering in cancer cells. This nuclease enters ruptured micronuclei—small cellular structures containing misplaced chromosomes—and fragments DNA, creating the chaotic genetic rearrangements characteristic of aggressive cancers. Analysis of over 10,000 cancer genomes confirmed that elevated N4BP2 expression correlates with chromothripsis and extrachromosomal DNA formation.
This discovery illuminates a critical mechanism underlying genome instability, one of cancer's defining features. The finding bridges two major cancer biology concepts: micronuclear rupture and chromothripsis, showing how mechanical chromosome displacement leads to enzymatic DNA destruction. For cancer research, N4BP2 represents both a potential therapeutic target and biomarker—its expression levels could predict which tumors harbor the most genomically unstable, treatment-resistant characteristics. The work also suggests that inhibiting N4BP2 might prevent the formation of extrachromosomal DNA circles that often carry oncogenes, offering a novel intervention point. However, since N4BP2 likely has normal cellular functions, therapeutic targeting would require precise understanding of its physiological roles to avoid unintended consequences.