Reference: Tsarin L and Shcherbakova PV (2025) PolED: a manually curated database of functional studies of POLE and POLD1 variants reported in humans. Database (Oxford) 2025

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Abstract


Human POLE and POLD1 genes encode DNA polymerases responsible for genome replication and proofreading of DNA synthesis errors. Germline and somatic POLE/POLD1 mutations compromising the polymerase fidelity cause cancers with high mutational burden. Ultramutation is associated with a better prognosis and immunotherapy response, highlighting the need to define tumour POLE/POLD1 status unambiguously. Prior studies assessed the functional significance of numerous POLE/POLD1 variants in experimental models. However, the data remain scattered and difficult to evaluate by non-specialists, limiting their utility for research and clinical applications. Through manual literature curation, we integrated data from functional studies of clinically relevant POLE and POLD1 variants into PolED, a publicly available database (https://poled-db.org). PolED compiles information on variant effects in biochemical assays, yeast, mammalian cells, and mouse tumour models along with supporting references. It also includes a concise summary of functional significance for each variant. PolED aims to assist in clinical decision-making, guide personalized therapy, and promote further research.

Reference Type
Journal Article
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Tsarin L, Shcherbakova PV
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