Journal
BIOESSAYS
Volume -, Issue -, Pages -Publisher
WILEY
DOI: 10.1002/bies.202300184
Keywords
DNA damage; genome stability; nuclear envelope; telomerase; telomere; telomere binding proteins
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Mammalian telomere-binding proteins TRF2 and RAP1 play a crucial role in protecting telomeres from aberrant recombination and interacting with the nuclear envelope to maintain chromosome stability.
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.
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