{"doi":"10.1101/2020.07.01.180455","title":"Oncogenic H-Ras Signaling Differentially Targets Replicative and Specialized DNA Polymerases for Depletion","abstract":"Abstract Oncogene activation significantly alters DNA replication dynamics, causing replication stress and genome instability. However, little is known about DNA polymerase expression and regulation during oncogene-induced replication stress. We discovered that the Pol α catalytic subunit, Pol δ, Pol η and Pol κ are all depleted in response to H-Ras G12V overexpression in multiple human cell lines. Distinct transcriptional and post-translational mechanisms mediate replicative and specialized DNA polymerase regulation, respectively, and include both MEK-dependent and -independent pathways. Moreover, Pol η depletion is sufficient to induce a senescence-like growth arrest in non-transformed cells. We provide evidence that H-Ras G12V -induced polymerase depletion contributes not only to oncogene-induced replication stress, but also to cell cycle checkpoint enforcement. Polymerase degradation is a protective response, associated with improved cell survival in the face of oncogene-induced stress. Our findings significantly impact our understanding of oncogene-induced cellular transformation and suggest that imbalanced polymerase levels may contribute to neoplastic progression.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":130323,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":557914,"name":"Raquel Buj","orcid":"0000-0002-8355-6666","position":1,"is_corresponding":false},{"id":314761,"name":"Katherine M. Aird","orcid":"0000-0002-5828-2325","position":2,"is_corresponding":false},{"id":501738,"name":"Julia M. Sidorova","orcid":"0000-0001-5502-4323","position":3,"is_corresponding":false},{"id":582647,"name":"Kristin A. Eckert","orcid":"0000-0002-8659-5062","position":4,"is_corresponding":false},{"id":582646,"name":"Wei-Chung Tsao","orcid":"0000-0002-4801-7333","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-18T23:15:53.196774Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}