| Literature DB >> 33673424 |
Elisa Mentegari1, Federica Bertoletti1, Miroslava Kissova1, Elisa Zucca1, Silvia Galli1, Giulia Tagliavini1, Anna Garbelli1, Antonio Maffia1, Silvia Bione1, Elena Ferrari2, Fabrizio d'Adda di Fagagna1,3, Sofia Francia1, Simone Sabbioneda1, Liuh-Yow Chen4, Joachim Lingner4, Valerie Bergoglio5, Jean-Sébastien Hoffmann6, Ulrich Hübscher2, Emmanuele Crespan1, Giovanni Maga1.
Abstract
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.Entities:
Keywords: DNA double-strand breaks (DSBs), extra-chromosomal telomeric repeats (ECTRs), promyelocytic leukemia (PML) bodies; alternative lengthening of telomeres (ALT), DNA polymerase λ; microhomology-mediated strand transfer (MMST) activity; telomere dysfunction-induced foci (TIFs), telomere stress
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Year: 2021 PMID： 33673424 PMCID： PMC7956399 DOI： 10.3390/ijms22052365
Source DB: PubMed Journal: Int J Mol Sci ISSN： 1422-0067 Impact factor: 6.208