A Role for Human DNA Polymerase λ in Alternative Lengthening of Telomeres.

Autor: Mentegari E; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Bertoletti F; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Kissova M; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Zucca E; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Galli S; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Tagliavini G; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Garbelli A; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Maffia A; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Bione S; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Ferrari E; Department of Molecular Mechanisms of Disease, University of Zürich-Irchel, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland., Fagagna FDD; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy.; IFOM-The FIRC Institute of Molecular Oncology, 20139 Milan, Italy., Francia S; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Sabbioneda S; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Chen LY; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Frontiers in Genetics National Center of Competence in Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, Switzerland., Lingner J; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Frontiers in Genetics National Center of Competence in Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, Switzerland., Bergoglio V; UMR1037 INSERM, Cancer Research Center of Toulouse, 2 Avenue Curien, 31037 Toulouse, France., Hoffmann JS; Laboratoire d'Excellence Toulouse Cancer (TOUCAN), Laboratoire de Pathologie, Institut Universitaire du Cancer-Toulouse, Oncopole, 1 avenue Irène-Joliot-Curie, 31059 Toulouse, France., Hübscher U; Department of Molecular Mechanisms of Disease, University of Zürich-Irchel, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland., Crespan E; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy., Maga G; Institute of Molecular Genetics IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, I-27100 Pavia, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Feb 27; Vol. 22 (5). Date of Electronic Publication: 2021 Feb 27.
DOI: 10.3390/ijms22052365
Abstrakt: Telomerase negative cancer cell types use the Alternative Lengthening of Telomeres (ALT) pathway to elongate telomeres ends. Here, we show that silencing human DNA polymerase (Pol λ) in ALT cells represses ALT activity and induces telomeric stress. In addition, replication stress in the absence of Pol λ, strongly affects the survival of ALT cells. In vitro, Pol λ can promote annealing of even a single G-rich telomeric repeat to its complementary strand and use it to prime DNA synthesis. The noncoding telomeric repeat containing RNA TERRA and replication protein A negatively regulate this activity, while the Protection of Telomeres protein 1 (POT1)/TPP1 heterodimer stimulates Pol λ. Pol λ associates with telomeres and colocalizes with TPP1 in cells. In summary, our data suggest a role of Pol λ in the maintenance of telomeres by the ALT mechanism.
Databáze: MEDLINE
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