{"doi":"10.1016/j.dnarep.2015.10.003","title":"Role of mismatch repair proteins in the processing of cisplatin interstrand cross-links","abstract":null,"journal":"DNA Repair","year":2015,"id":605679,"datarank":0.6766289259775276,"base_score":4.51085950651685,"endowment":4.51085950651685,"self_citation_contribution":0.6766289259775276,"citation_network_contribution":0.0,"self_endowment_contribution":0.6766289259775276,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":90,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":339487,"name":"Anbarasi Kothandapani","orcid":"0000-0001-9701-0800","position":1,"is_corresponding":false},{"id":848496,"name":"Anatoly Zhitkovich","orcid":"0000-0001-9007-2400","position":2,"is_corresponding":false},{"id":285722,"name":"Robert W. Sobol","orcid":"0000-0001-7385-3563","position":3,"is_corresponding":false},{"id":301321,"name":"Steve M. Patrick","orcid":"0000-0003-3325-6750","position":4,"is_corresponding":false},{"id":388840,"name":"Akshada Sawant","orcid":"0000-0001-9878-4445","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Role of mismatch repair proteins in the processing of cisplatin interstrand cross-links","abstract":"Mismatch repair (MMR) deficiency gives rise to cisplatin resistance and can lead to poor prognosis in cancers. Various models have been proposed to explain this low level of resistance caused due to loss of MMR proteins. We have shown that MMR proteins are required to maintain cisplatin interstrand cross-links (ICLs) on the DNA leading to increased cellular sensitivity. In our previous studies, we have shown that BER processing of the cisplatin ICLs is mutagenic. Polymerase β (Polβ) can generate mismatches which leads to the activation and the recruitment of mismatch repair proteins. In this paper, we distinguished between the requirement of different downstream MMR proteins for maintaining cisplatin sensitivity. We show that the MutSα (MSH2-MSH6) heterocomplex is required to maintain cisplatin sensitivity, whereas the Mutsβ complex has no effect. These results can be correlated with the increased repair of cisplatin ICLs and ICL induced DNA double strand breaks (DSBs) in the resistant cells. Moreover, we show that MLH1 proficient cells displayed a cisplatin sensitive phenotype when compared with the MLH1 deficient cells and the ATPase activity of MLH1 is essential to mediate this effect. Based on these results, we propose that MutSα as well as the downstream MMR pathway proteins are essential to maintain a cisplatin sensitive phenotype as a consequence of processing Polβ induced mismatches at sites flanking cisplatin ICLs.","is_dataset_classified":null,"base_score":4.51085950651685,"endowment":4.51085950651685,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26519826","pmcid":"PMC4651805","openalex_id":"https://openalex.org/W1817322973","authors":[],"funders":[{"funder_name":"NIEHS NIH HHS","grant_id":"ES008786","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"R01 ES008786","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM088249","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA148629","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM088249","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA148629","title":null}],"total_grants":6,"fwci":4.6332,"citation_percentile":0.95143457,"influential_citations":0,"citation_trend":[{"year":2016,"count":4},{"year":2017,"count":9},{"year":2018,"count":9},{"year":2019,"count":3},{"year":2020,"count":7},{"year":2021,"count":9},{"year":2022,"count":14},{"year":2023,"count":11},{"year":2024,"count":9},{"year":2025,"count":10},{"year":2026,"count":5}],"oa_status":"green","license":"https://doi.org/10.15223/policy-004","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4651805","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4651805","host_type":"repository"},{"url":"https://api.elsevier.com/content/article/PII:S1568786415001986?httpAccept=text/plain","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1568786415001986?httpAccept=text/xml","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.dnarep.2015.10.003","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26519826","host_type":"repository"}],"fields_of_study":["Genetic factors in colorectal cancer","DNA Repair Mechanisms","RNA Research and Splicing"],"mesh_terms":["MutL Protein Homolog 1","Animals","Antineoplastic Agents","Cisplatin","Cross-Linking Reagents","DNA-Binding Proteins","Humans","Nuclear Proteins","Drug Resistance, Neoplasm","Cell Line, Tumor","Adaptor Proteins, Signal Transducing","Mice","MutS Homolog 2 Protein","DNA Mismatch Repair","DNA Breaks, Double-Stranded","Gene Knockdown Techniques"],"keywords":["Biology","Cisplatin","DNA mismatch repair","Computational biology","Genetics","DNA repair","Cell biology","DNA","Chemotherapy","Resistance","ATPase","Mmr","Ber"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T03:00:42.284830Z","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":[]}