CtIP is essential for telomere replication

Nucleic Acids Research
Susanna StroikEric A Hendrickson

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.

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Citations

Oct 11, 2019·International Journal of Molecular Sciences·Pauline Billard, Delphine A Poncet
Apr 8, 2020·International Journal of Molecular Sciences·Quratul AinAlexandra Kretz
Feb 6, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zizhen SiXidi Wang
Mar 17, 2020·Current Opinion in Genetics & Development·Susanna Stroik, Eric A Hendrickson
Jul 11, 2020·DNA Repair·Susanna Stroik, Eric A Hendrickson
Sep 21, 2020·Seminars in Cell & Developmental Biology·Nour L MozaffariAlessandro A Sartori
Jul 30, 2021·Frontiers in Cell and Developmental Biology·Stephanie M AckersonJason A Stewart
Sep 1, 2021·Current Opinion in Genetics & Development·Erica J Polleys, Catherine H Freudenreich

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Methods Mentioned

BETA
electrophoresis
protein assay
PCR
Dot blot

Software Mentioned

Fiji

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