Telomere maintenance critically depends on the distinct activities of telomerase, which adds telomeric repeats to solve the end replication problem, and RTEL1, which dismantles DNA secondary structures at telomeres to facilitate replisome progression. Here, we establish that reversed replication forks are a pathological substrate for telomerase and the source of telomere catastrophe in Rtel1-/- cells. Inhibiting telomerase recruitment to telomeres, but not its activity, or blocking replication fork reversal through PARP1 inhibition or depleting UBC13 or ZRANB3 prevents the rapid accumulation of dysfunctional telomeres in RTEL1-deficient cells. In this context, we establish that telomerase binding to reversed replication forks inhibits telomere replication, which can be mimicked by preventing replication fork restart through depletion of RECQ1 or PARG. Our results lead us to propose that telomerase inappropriately binds to and inhibits restart of reversed replication forks within telomeres, which compromises replication and leads to critically short telomeres.
Pubmed ID: 29290468 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Commercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsA commercial graphing software company that offers scientific software for statistical analyses, curve fitting and data analysis. It offers four programs: Prism, InStat, StatMate and QuickCalcs.
View all literature mentionsBiotechnology company focused on developing robust gene delivery products, by using its proprietary technologies. Since 2004, we have worked with over 300 research labs in 20 different countries to provide gene delivery products and services using many viral platforms including recombinant adenoviruses, adeno-associated virus (AAV) and lentivirus.
View all literature mentionsAn Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.
View all literature mentionsAn Antibody supplier; Dako was purchased by Agilent in 2012 and several years later the websites began to reflect the Dako products as part of the Agilent catalog.
View all literature mentionsThis polyclonal targets ZRANB3
View all literature mentionsThis polyclonal targets TERT
View all literature mentionsThis monoclonal targets BrdU (BU1/75 ICR1)
View all literature mentionsThis polyclonal targets Ube2n
View all literature mentionsThis polyclonal targets TRF1
View all literature mentionsThis polyclonal targets RAD51
View all literature mentionsThis polyclonal targets Rad51
View all literature mentionsThis monoclonal targets BTBD12 (H-39)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets alpha-Tubulin antibody produced in mouse
View all literature mentionsThis monoclonal targets Telomerase reverse transcriptase
View all literature mentionsThis monoclonal targets PCNA (PC10)
View all literature mentionsThis monoclonal targets PARP-1 (C2-10)
View all literature mentionsThis monoclonal targets Poly(ADP-ribose)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentions3D image analysis software to visualize, analyze and validate 3D fluorescence images from a wide range of confocal microscopy, widefield and high content screening systems. It is fully integrated for a seamless user experience.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsThis monoclonal targets BrdU (BU1/75 ICR1)
View all literature mentionsThis polyclonal targets Ube2n
View all literature mentionsThis polyclonal targets TRF1
View all literature mentionsThis polyclonal targets RAD51
View all literature mentionsThis polyclonal targets Rad51
View all literature mentionsThis monoclonal targets BTBD12 (H-39)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets alpha-Tubulin antibody produced in mouse
View all literature mentionsThis monoclonal targets Telomerase reverse transcriptase
View all literature mentionsThis monoclonal targets PCNA (PC10)
View all literature mentionsThis monoclonal targets PARP-1 (C2-10)
View all literature mentionsThis monoclonal targets Poly(ADP-ribose)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentions