TRF2 Mediates Replication Initiation within Human Telomeres to Prevent Telomere Dysfunction.

ABSTRACT: The telomeric shelterin protein telomeric repeat-binding factor 2 (TRF2) recruits origin recognition complex (ORC) proteins, the foundational building blocks of DNA replication origins, to telomeres. We seek to determine whether TRF2-recruited ORC proteins give rise to functional origins in telomere repeat tracts. We find that reduction of telomeric recruitment of ORC2 by expression of an ORC interaction-defective TRF2 mutant significantly reduces telomeric initiation events in human cells. This reduction in initiation events is accompanied by telomere repeat loss, telomere aberrations and dysfunction. We demonstrate that telomeric origins are activated by induced replication stress to provide a key rescue mechanism for completing compromised telomere replication. Importantly, our studies

SUBMITTER: Drosopoulos WC 

PROVIDER: S-EPMC7790361 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature