DNA replication is complex and highly regulated, and DNA replication errors can lead to human diseases such as cancer. DNA polymerase ε (polε) is a key player in DNA replication and contains a large subunit called POLE, which possesses both a DNA polymerase domain and a 3'-5' exonuclease domain (EXO). Mutations at the EXO domain and other missense mutations on POLE with unknown significance have been detected in a variety of human cancers. Based on cancer genome databases, Meng and colleagues (pp. 74-79) previously identified several missense mutations in POPS (pol2 family-specific catalytic core peripheral subdomain), and mutations at the conserved residues of yeast Pol2 (pol2-REL) showed reduced DNA synthesis and growth. In this issue of Genes & Development, Meng and colleagues (pp. 74-79) found unexpectedly that mutations at the EXO domain rescue the growth defects of pol2-REL. They further discovered that EXO-mediated polymerase backtracking impedes forward movement of the enzyme when POPS is defective, revealing a novel interplay between the EXO domain and POPS of Pol2 for efficient DNA synthesis. Additional molecular insight into this interplay will likely inform the impact of cancer-associated mutations found in both the EXO domain and POPS on tumorigenesis and uncover future novel therapeutic strategies.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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Evidence ID | Analyze ID | File | Description |
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