{"doi":"10.1016/j.dnarep.2021.103231","title":"Structure, function and evolution of the Helix-hairpin-Helix DNA glycosylase superfamily: Piecing together the evolutionary puzzle of DNA base damage repair mechanisms","abstract":"The Base Excision Repair (BER) pathway is a highly conserved DNA repair system targeting chemical base modifications that arise from oxidation, deamination and alkylation reactions. BER features lesion-specific DNA glycosylases (DGs) which recognize and excise modified or inappropriate DNA bases to produce apurinic/apyrimidinic (AP) sites and coordinate AP-site hand-off to subsequent BER pathway enzymes. The DG superfamilies identified have evolved independently to cope with a wide variety of nucleobase chemical modifications. Most DG superfamilies recognize a distinct set of structurally related lesions. In contrast, the Helix-hairpin-Helix (HhH) DG superfamily has the remarkable ability to act upon structurally diverse sets of base modifications. The versatility in substrate recognition of the HhH-DG superfamily has been shaped by motif and domain acquisitions during evolution. In this paper, we review the structural features and catalytic mechanisms of the HhH-DG superfamily and draw a hypothetical reconstruction of the evolutionary path where these DGs developed diverse and unique enzymatic features.","journal":"DNA repair","year":2021,"id":159891,"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":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9664,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":671895,"name":"Merve Demir","orcid":"0000-0002-5721-8268","position":1,"is_corresponding":false},{"id":672973,"name":"Wen-Jen Lin","orcid":null,"position":2,"is_corresponding":false},{"id":379467,"name":"Sheila S. David","orcid":"0000-0001-5873-7935","position":3,"is_corresponding":false},{"id":671894,"name":"Carlos H. Trasviña‐Arenas","orcid":"0000-0002-9881-375X","position":0,"is_corresponding":true}],"reference_count":168,"raw_metadata":null,"created_at":"2026-07-18T23:44:43.908634Z","pmid":"34649144","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":[]}