Interstitial telomeric sequences promote gross chromosomal rearrangement via multiple mechanisms.

ABSTRACT: Telomeric DNA sequences are difficult to replicate. Replication forks frequently pause or stall at telomeres, which can lead to telomere truncation and dysfunction. In addition to being at chromosome ends, telomere repeats are also present at internal locations within chromosomes, known as interstitial telomeric sequences (ITSs). These sequences are unstable and prone to triggering gross chromosomal rearrangements (GCRs). In this study, we quantitatively examined the effect of ITSs on the GCR rate in Saccharomyces cerevisiae using a genetic assay. We find that the GCR rate increases exponentially with ITS length. This increase can be attributed to the telomere repeat binding protein Rap1 impeding DNA replication and a bias of repairing DNA breaks at or distal to the ITS via de novo

SUBMITTER: Rosas Bringas FR 

PROVIDER: S-EPMC11626172 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature