ArticleMolecular and cellular biology2005
Alterations of DNA and chromatin structures at telomeres and genetic instability in mouse cells defective in DNA polymerase alpha.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- The yeast CST and Polα/primase complexes act in concert to ensure proper telomere maintenance and protection.Nucleic acids research · 2025Article
- CST-Polα/Primase: the second telomere maintenance machine.Genes & development · 2023Review
- Defective DNA Polymerase α-Primase Leads to X-Linked Intellectual Disability Associated with Severe Growth Retardation, Microcephaly, and Hypogonadism.American journal of human genetics · 2019Article
- CTC1-STN1 terminates telomerase while STN1-TEN1 enables C-strand synthesis during telomere replication in colon cancer cells.Nature communications · 2018Article
- A POT1 mutation implicates defective telomere end fill-in and telomere truncations in Coats plus.Genes & development · 2016Article
- DNA-Directed Polymerase Subunits Play a Vital Role in Human Telomeric Overhang Processing.Molecular cancer research : MCR · 2015Article
- The presence of telomere fusion in sporadic colon cancer independently of disease stage, TP53/KRAS mutation status, mean telomere length, and telomerase activity.Neoplasia (New York, N.Y.) · 2014Article
- A human artificial chromosome recapitulates the metabolism of native telomeres in mammalian cells.PloS one · 2014Article
- Functional characterization of human CTC1 mutations reveals novel mechanisms responsible for the pathogenesis of the telomere disease Coats plus.Aging cell · 2013Article
- Identification of telomere-associated molecules by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP).Scientific reports · 2013Article
- Telomere-end processing: mechanisms and regulation.Chromosoma · 2013Article
- Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools.Environmental and molecular mutagenesis · 2012Review
- Partial complementation of a DNA ligase I deficiency by DNA ligase III and its impact on cell survival and telomere stability in mammalian cells.Cellular and molecular life sciences : CMLS · 2012Article
- Telomere replication: poised but puzzling.Journal of cellular and molecular medicine · 2011Review
- DNA replication fidelity and cancer.Seminars in cancer biology · 2010Review
- Aberrant DNA polymerase alpha is excluded from the nucleus by defective import and degradation in the nucleus.The Journal of biological chemistry · 2009Article
- Article
- Effect of dehydroaltenusin-C12 derivative, a selective DNA polymerase alpha inhibitor, on DNA replication in cultured cells.Molecules (Basel, Switzerland) · 2008Article
- Telomere length homeostasis.Chromosoma · 2006Review
- Cell-cycle-dependent Xenopus TRF1 recruitment to telomere chromatin regulated by Polo-like kinase.The EMBO journal · 2006Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Telomere length is controlled by a homeostatic mechanism that involves telomerase, telomere-associated proteins, and conventional replication machinery. Specifically, the coordinated actions of the lagging strand synthesis and telomerase have been argued. Although DNA polymerase alpha, an enzyme important for the lagging strand synthesis, has been indicated to function in telomere metabolism in yeasts and ciliates, it has not been characterized in higher eukaryotes. Here, we investigated the impact of compromised polymerase alpha activity on telomeres, using tsFT20 mouse mutant cells harboring a temperature-sensitive polymerase alpha mutant allele. When polymerase alpha was temperature-inducibly inactivated, we observed sequential events that included an initial extension of the G-tail followed by a marked increase in the overall telomere length occurring in telomerase-independent and -dependent manners, respectively. These alterations of telomeric DNA were accompanied by alterations of telomeric chromatin structures as revealed by quantitative chromatin immunoprecipitation and immunofluorescence analyses of TRF1 and POT1. Unexpectedly, polymerase alpha inhibition resulted in a significantly high incidence of Robertsonian chromosome fusions without noticeable increases in other types of chromosomal aberrations. These results indicate that although DNA polymerase alpha is essential for genome-wide DNA replication, hypomorphic activity leads to a rather specific spectrum of chromosomal abnormality.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.