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A Role for Human DNA Polymerase λ in Alternative Lengthening of Telomeres
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, MDPI, 2021, 22 (5), pp.2365. ⟨10.3390/ijms22052365⟩, International Journal of Molecular Sciences, Vol 22, Iss 2365, p 2365 (2021), Volume 22, Issue 5
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- International audience; 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.
- Subjects :
- Telomerase
Telomeric repeat-containing RNAs
[SDV]Life Sciences [q-bio]
viruses
promyelocytic leukemia (PML) bodies
Aminopeptidases
alternative lengthening of telomeres (ALT)
Shelterin Complex
lcsh:Chemistry
0302 clinical medicine
Replication Protein A
microhomology-mediated strand transfer (MMST) activity
lcsh:QH301-705.5
Spectroscopy
Polymerase
0303 health sciences
biology
extra-chromosomal telomeric repeats (ECTRs)
Chemistry
alternative lengthening of telomeres (ALT), DNA polymerase λ
General Medicine
Telomere
DNA double-strand breaks (DSBs), extra-chromosomal telomeric repeats (ECTRs), promyelocytic leukemia (PML) bodies
Computer Science Applications
Cell biology
030220 oncology & carcinogenesis
telomere stress
Telomere-Binding Proteins
[SDV.CAN]Life Sciences [q-bio]/Cancer
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Complementary DNA
Cell Line, Tumor
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
DNA double-strand breaks (DSBs)
Gene silencing
Humans
Physical and Theoretical Chemistry
Molecular Biology
Replication protein A
telomere dysfunction-induced foci (TIFs), telomere stress
DNA Polymerase beta
030304 developmental biology
DNA synthesis
Organic Chemistry
Telomere Homeostasis
G-Quadruplexes
lcsh:Biology (General)
lcsh:QD1-999
DNA polymerase λ
Multiprotein Complexes
biology.protein
telomere dysfunction-induced foci (TIFs)
Serine Proteases
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, MDPI, 2021, 22 (5), pp.2365. ⟨10.3390/ijms22052365⟩, International Journal of Molecular Sciences, Vol 22, Iss 2365, p 2365 (2021), Volume 22, Issue 5
- Accession number :
- edsair.doi.dedup.....04c5142fb9ab19ec3f96dfa6f03a9527