ArticleProceedings of the National Academy of Sciences of the United States of America2020
Polymerase δ promotes chromosomal rearrangements and imprecise double-strand break repair.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- ERCC6 at the Transcription-Replication Interface: Integration of Transcription-Coupled Repair with Replication Stress Responses.International journal of molecular sciences · 2026Review
- β-Elemene Rescues Radiation-Induced Enteritis by Orchestrating a Host-Microbiome Circuit That Fuels Epigenetic DNA Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- DNA Polymerase Delta 2 Activates Cell Cycle in Lung Adenocarcinoma, Leading to High Malignancy and Poor Prognosis.Annals of surgical oncology · 2025Article
- ASO Author Reflections: Clinical and Biological Significance of POLD2 in Lung Adenocarcinoma.Annals of surgical oncology · 2025Article
- In vivo CRISPR-Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington's disease.Nature genetics · 2025Article
- Beyond proofreading: POLD1 mutations as dynamic orchestrators of genomic instability and immune evasion in cancer.Frontiers in immunology · 2025Review
- Mechanisms of tandem duplication in the cancer genome.DNA repair · 2025Review
- POLD3 as Controller of Replicative DNA Repair.International journal of molecular sciences · 2024Review
- Human Autosomal Recessive DNA Polymerase Delta 3 Deficiency Presenting as Omenn Syndrome.Journal of clinical immunology · 2023Article
- Article
- POLD4 Promotes Glioma Cell Proliferation and Suppressive Immune Microenvironment: A Pan-Cancer Analysis Integrated with Experimental Validation.International journal of molecular sciences · 2023Article
- Saccharomyces cerevisiae DNA polymerase IV overcomes Rad51 inhibition of DNA polymerase δ in Rad52-mediated direct-repeat recombination.Nucleic acids research · 2023Article
- Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2Nature communications · 2023Article
- Interaction of human HelQ with DNA polymerase delta halts DNA synthesis and stimulates DNA single-strand annealing.Nucleic acids research · 2023Article
- Multifaceted Nature of DNA Polymerase θ.International journal of molecular sciences · 2023Review
- Critical DNA damaging pathways in tumorigenesis.Seminars in cancer biology · 2022Review
- Alternative end-joining in BCR gene rearrangements and translocations.Acta biochimica et biophysica Sinica · 2022Review
- Mechanism, cellular functions and cancer roles of polymerase-theta-mediated DNA end joining.Nature reviews. Molecular cell biology · 2022Review
- An integrative analysis revealing POLD2 as a tumor suppressive immune protein and prognostic biomarker in pan-cancer.Frontiers in genetics · 2022Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Recent studies have implicated DNA polymerases θ (Pol θ) and β (Pol β) as mediators of alternative nonhomologous end-joining (Alt-NHEJ) events, including chromosomal translocations. Here we identify subunits of the replicative DNA polymerase δ (Pol δ) as promoters of Alt-NHEJ that results in more extensive intrachromosomal mutations at a single double-strand break (DSB) and more frequent translocations between two DSBs. Depletion of the Pol δ accessory subunit POLD2 destabilizes the complex, resulting in degradation of both POLD1 and POLD3 in human cells. POLD2 depletion markedly reduces the frequency of translocations with sequence modifications but does not affect the frequency of translocations with exact joins. Using separation-of-function mutants, we show that both the DNA synthesis and exonuclease activities of the POLD1 subunit contribute to translocations. As described in yeast and unlike Pol θ, Pol δ also promotes homology-directed repair. Codepletion of POLD2 with 53BP1 nearly eliminates translocations. POLD1 and POLD2 each colocalize with phosphorylated H2AX at ionizing radiation-induced DSBs but not with 53BP1. Codepletion of POLD2 with either ligase 3 (LIG3) or ligase 4 (LIG4) does not further reduce translocation frequency compared to POLD2 depletion alone. Together, these data support a model in which Pol δ promotes Alt-NHEJ in human cells at DSBs, including translocations.
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