Telomeres cooperate with the nuclear envelope to maintain genome stability

• Published in: BioEssays Vol. 46; no. 2; pp. e2300184 - n/a
• Main Authors: Rai, Rekha, Sodeinde, Tori, Boston, Ava, Chang, Sandy
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-02-2024
• Subjects: Animals; Binding; Chromosomes; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA damage; DNA repair; genome stability; Genomes; Genomic Instability; Homeostasis; Homology; Humans; Lamins; Mammals; Mammals - genetics; nuclear envelope; Nuclear Envelope - metabolism; Proteins; Rap1 protein; Recombination; Stability; telomerase; telomere; Telomere - genetics; Telomere - metabolism; telomere binding proteins; Telomere-binding protein; Telomere-Binding Proteins - chemistry; Telomere-Binding Proteins - genetics; Telomere-Binding Proteins - metabolism; Telomeres; TRF2 protein; nuclear envelope; genome stability; telomerase; telomere binding proteins; DNA damage; telomere
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.202300184

Mammalian telomeres have evolved safeguards to prevent their recognition as DNA double‐stranded breaks by suppressing the activation of various DNA sensing and repair proteins. We have shown that the telomere‐binding proteins TRF2 and RAP1 cooperate to prevent telomeres from undergoing aberrant homology‐directed recombination by mediating t‐loop protection. Our recent findings also suggest that mammalian telomere‐binding proteins interact with the nuclear envelope to maintain chromosome stability. RAP1 interacts with nuclear lamins through KU70/KU80, and disruption of RAP1 and TRF2 function result in nuclear envelope rupture, promoting telomere‐telomere recombination to form structures termed ultrabright telomeres. In this review, we discuss the importance of the interactions between shelterin components and the nuclear envelope to maintain telomere homeostasis and genome stability.
Our research has shown that the telomere‐binding proteins TRF2 and RAP1 cooperate to prevent the formation of ultrabright telomeres (UT) and suggests that telomere‐binding proteins interact with the nuclear envelope and nuclear lamins to maintain chromosome stability. Both components are critical for the maintenance of telomere homeostasis and genome stability.