Article

 

Telomere Replication Stress Induced by POT1 Inactivation Accelerates Tumorigenesis. Public Deposited

https://scholar.colorado.edu/concern/articles/8p58pd626
Abstract
  • Genome sequencing studies have revealed a number of cancer-associated mutations in the telomere-binding factor POT1. Here, we show that when combined with p53 deficiency, depletion of murine POT1a in common lymphoid progenitor cells fosters genetic instability, accelerates the onset, and increases the severity of T cell lymphomas. In parallel, we examined human and mouse cells carrying POT1 mutations found in cutaneous T cell lymphoma (CTCL) patients. Inhibition of POT1 activates ATR-dependent DNA damage signaling and induces telomere fragility, replication fork stalling, and telomere elongation. Our data suggest that these phenotypes are linked to impaired CST (CTC1-STN1-TEN1) function at telomeres. Lastly, we show that proliferation of cancer cells lacking POT1 is enabled by the attenuation of the ATR kinase pathway. These results uncover a role for defective telomere replication during tumorigenesis.
Creator
Date Issued
  • 2016-06-07
Academic Affiliation
Journal Title
Journal Issue/Number
  • 10
Journal Volume
  • 15
File Extent
  • 2170-2184
Subject
Last Modified
  • 2019-12-05
Identifier
  • PubMed ID: 27239034
Resource Type
Rights Statement
DOI
ISSN
  • 2211-1247
Language

Relationships

Items