Dataset Information

Human POT1 Prevents Severe Telomere Damage Instability Induced by Homology Directed DNA Repair

ABSTRACT: The evolutionarily conserved POT1 protein binds the single stranded G-rich telomeric DNA and has been implicated in telomeric DNA maintenance and the suppression of DNA damage checkpoint signaling. Here, we explore human POT1 function through genetics and proteomics discovering that the complete absence of POT1 leads to severe telomere maintenance defects that had not been anticipated from previous depletion studies. We determine the telomeric proteome upon POT1-loss by implementing an improved telomeric chromatin isolation protocol. Using quantitative proteomics by tandem mass tags (TMT) we identified a large set of proteins involved in nucleic acid metabolism that engage with telomeres upon loss of POT1. Inactivation of the homology directed repair machinery suppresses POT1-loss mediated telomeric DNA defects. Our results unravel as major function of human POT1 the suppression of telomere instability induced by homology directed repair.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Manfredo Quadroni

LAB HEAD: Joachim Lingner

PROVIDER: PXD016826 | Pride | 2020-10-21

REPOSITORIES: Pride

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			Action	DRS
	181129_Glousker_10919_OFFGEL_01.raw	Raw
	181129_Glousker_10919_OFFGEL_02.raw	Raw
	181129_Glousker_10919_OFFGEL_03.raw	Raw
	181129_Glousker_10919_OFFGEL_04.raw	Raw
	181129_Glousker_10919_OFFGEL_05.raw	Raw

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Publications

Human shelterin protein POT1 prevents severe telomere instability induced by homology-directed DNA repair.

Glousker Galina G Briod Anna-Sophia AS Quadroni Manfredo M Lingner Joachim J

The EMBO journal 20201019 23

The evolutionarily conserved POT1 protein binds single-stranded G-rich telomeric DNA and has been implicated in contributing to telomeric DNA maintenance and the suppression of DNA damage checkpoint signaling. Here, we explore human POT1 function through genetics and proteomics, discovering that a complete absence of POT1 leads to severe telomere maintenance defects that had not been anticipated from previous depletion studies in human cells. Conditional deletion of POT1 in HEK293E cells gives r ...[more]

PMID: 33073402

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