Elucidation of the telomeric proteome by QTIP

A fundamental aspect of telomeres is the complexity of their composition and their dynamic nature. To tackle the molecular changes that occur at telomeres during normal development, in cancer and in telomere syndromes, we established a Quantitative Telomeric chromatin Isolation Protocol (QTIP), which allows the biochemical isolation and analysis of the telomeric nucleoprotein complexes. Combined with SILAC or TMT labeling and mass spectrometry, the QTIP technique enables comparison of different physiological and pathological telomeric states. Our analysis uncovered novel telomeric factors that associate with intact or damaged telomeres. Recently, we also adapted the QTIP method to determine the composition of the telomeric replisome and the mechanisms of telomere replication.

Publications related to this project

A quantitative telomeric chromatin isolation protocol identifies different telomeric states
*Grolimund L, *Aeby E, Hamelin R, Armand F, Chiappe D, Moniatte M, Lingner J.
Nature Communications. 2013. doi: 10.1038/ncomms3848.
The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening
*Pfeiffer V, *Crittin J, Grolimund L, Lingner J.
EMBO J. 2013. doi: 10.1038/emboj.2013.217.
Peroxiredoxin 1 Protects Telomeres from Oxidative Damage and Preserves Telomeric DNA for Extension by Telomerase
*Aeby E, *Ahmed W, Redon S, Simanis S, Lingner J.
Cell Reports. 2016. doi: 10.1016/j.celrep.2016.11.071.
Quantitative telomeric chromatin isolation protocol for human cells
Majerská J, Redon S, Lingner J. 
Methods. 2017. doi: 10.1016/j.ymeth.2016.08.003.
The telomeric DNA damage response occurs in the absence of chromatin decompaction.
Vancevska A, Douglass KM, Pfeiffer V, Manley S, Lingner J.
Genes Dev. doi: 10.1101/gad.294082.116.
PRDX1 and MTH1 cooperate to prevent ROS-mediated inhibition of telomerase
Ahmed W, Lingner J.
Genes & Development. 2018. doi: 10.1101/gad.313460.118.
Transformation-induced stress at telomeres is counteracted through changes in the telomeric proteome including SAMHD1
Majerska J, Feretzaki M, Glousker G, Lingner J.
Life Science Alliance. 2018. doi: 10.26508/lsa.201800121.
SMCHD1 promotes ATM-dependent DNA damage signaling and repair of uncapped telomeres.

Vančevska A, Ahmed W, Pfeiffer V, Feretzaki M, Boulton SJ, Lingner J.
EMBO J. 2020. doi: 10.15252/embj.2019102668.
Human shelterin protein POT1 prevents severe telomere instability induced by homology-directed DNA repair.
Glousker G, Briod AS, Quadroni M, Lingner J.
EMBO J. 2020. doi: 10.15252/embj.2020104500.
The human telomeric proteome during telomere replication.
*Lin CG, *Näger AC, Lunardi T, Vančevska A, **Lossaint G, **Lingner J.
Nucleic Acids Res. 2021. doi: 10.1093/nar/gkab1015.