CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy

Significance CENP-A, the histone H3 variant that forms a unique centromeric chromatin, is essential for faithful chromosome segregation during mitosis. Inability to connect centromere mitotic spindle causes aneuploidy, hallmark of many cancers. In addition missegregation, fusions at (peri)centromeres are prevalent in cancers, but how such rearrangements arise remains unclear. Here, we identified role CENP-A maintaining integrity centromere-associated repetitive sequences by ensuring their effective replication human cells. absence generation DNA–RNA hybrids due transcription–replication conflicts delayed DNA replication, breakage, recombination, and translocations centromeres. Centromeres thus possess special mechanism facilitate suppress translocations.