CtIP is essential for telomere replication

Susanna Stroik, Kevin Kurtz, Eric A Hendrickson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The maintenance of telomere length is critical to longevity and survival. Specifically, the failure to properly replicate, resect, and/or form appropriate telomeric structures drives telomere shortening and, in turn, genomic instability. The endonuclease CtIP is a DNA repair protein that is well-known to promote genome stability through the resection of endogenous DNA double-stranded breaks. Here, we describe a novel role for CtIP. We show that in the absence of CtIP, human telomeres shorten rapidly to non-viable lengths. This telomere dysfunction results in an accumulation of fusions, breaks, and frank telomere loss. Additionally, CtIP suppresses the generation of circular, extrachromosomal telomeric DNA. These latter structures appear to arise from arrested DNA replication forks that accumulate in the absence of CtIP. Hence, CtIP is required for faithful replication through telomeres via its roles at stalled replication tracts. Our findings demonstrate a new role for CtIP as a protector of human telomere integrity.

Original languageEnglish (US)
Pages (from-to)8927-8940
Number of pages14
JournalNucleic acids research
Volume47
Issue number17
DOIs
StatePublished - Sep 26 2019

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Telomere
Telomere Shortening
Genomic Instability
Telomere Homeostasis
Double-Stranded DNA Breaks
Endonucleases
DNA Replication
DNA Repair
Survival
DNA
Proteins

Cite this

CtIP is essential for telomere replication. / Stroik, Susanna; Kurtz, Kevin; Hendrickson, Eric A.

In: Nucleic acids research, Vol. 47, No. 17, 26.09.2019, p. 8927-8940.

Research output: Contribution to journalArticle

Stroik, Susanna ; Kurtz, Kevin ; Hendrickson, Eric A. / CtIP is essential for telomere replication. In: Nucleic acids research. 2019 ; Vol. 47, No. 17. pp. 8927-8940.
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