Replication Fork Stability Is Essential for the Maintenance of Centromere Integrity in the Absence of Heterochromatin

SummaryThe centromere of many eukaryotes contains highly repetitive sequences marked by methylation of histone H3K9 by Clr4KMT1. This recruits multiple heterochromatin proteins, including Swi6 and Chp1, to form a rigid centromere and ensure accurate chromosome segregation. In the absence of heterochromatin, cells show an increased rate of recombination in the centromere, as well as chromosome loss. These defects are severely aggravated by loss of replication fork stability. Thus, heterochromatin proteins and replication fork protection mechanisms work in concert to prevent abnormal recombination, preserve centromere integrity, and ensure faithful chromosome segregation.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Fork protection complex protects centromeric repeats when heterochromatin is lost ► Mutants lacking heterochromatin and fork protection exhibit increased recombination ► Prolonged condensation in mutants lacking both heterochromatin and fork protection