{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRMI1 is an evolutionarily conserved component of the BLM–topoisomerase IIIα complex that plays a pivotal role in the processing of homologous recombination intermediates. By promoting the dissolution of double Holliday junctions into noncrossover products, RMI1 helps channel recombination repair toward genome‐stabilizing pathways. Structural and biochemical studies have elucidated that RMI1 contains OB‐fold domains and specific insertion motifs that mediate interactions with both BLM and Topo IIIα, thereby recruiting and enhancing the decatenase activity required for strand–passage reactions. Single–molecule and yeast–based investigations further demonstrate that RMI1 modulates the architecture of the TRR complex, ensuring efficient dissolution of toxic recombination intermediates."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in recombination, RMI1 is integral to the response to replication stress. By enhancing the DNA unwinding activity of BLM, RMI1 contributes to efficient DNA end resection and promotes replication fork progression under stress conditions. Furthermore, RMI1 facilitates the proper loading of repair proteins such as RAD51, thereby ensuring efficient recovery from replication perturbations and guarding against fork collapse and radiosensitivity. These findings, based on reconstituted systems and single–molecule imaging, underscore the importance of RMI1 as part of the TOP3A–RMI1–RMI2 ensemble in maintaining the integrity of DNA replication processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its direct functions in DNA repair and replication, RMI1 plays broader roles in genome stability and cell cycle regulation. Genetic and clinical studies have linked RMI1 polymorphisms and altered expression to increased cancer susceptibility, including risks for prostate cancer, hematological malignancies, and other tumors. Moreover, RMI1 undergoes post–translational modifications—such as phosphorylation during mitosis—that are critical for its function in the spindle assembly checkpoint and accurate chromosome segregation. Collectively, these observations highlight RMI1 as a key guardian that restricts aberrant homologous recombination, maintains chromosomal integrity, and thereby prevents tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Leonard Wu, Csanad Z Bachrati, Jiongwen Ou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0508295103"}], "href": "https://doi.org/10.1073/pnas.0508295103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16537486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16537486"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Steven Raynard, Wendy Bussen, Patrick Sung "}, {"type": "b", "children": [{"type": "t", "text": "A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C600051200"}], "href": "https://doi.org/10.1074/jbc.C600051200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16595695"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16595695"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wendy Bussen, Steven Raynard, Valeria Busygina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Holliday junction processing activity of the BLM-Topo IIIalpha-BLAP75 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M706116200"}], "href": "https://doi.org/10.1074/jbc.M706116200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17728255"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17728255"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Steven Raynard, Weixing Zhao, Wendy Bussen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional role of BLAP75 in BLM-topoisomerase IIIalpha-dependent holliday junction processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M802127200"}], "href": "https://doi.org/10.1074/jbc.M802127200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18390547"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18390547"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jay Yang, Csanad Z Bachrati, Jiongwen Ou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.123216"}], "href": "https://doi.org/10.1074/jbc.M110.123216"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20445207"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20445207"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Feng Wang, Yuting Yang, Thiyam Ramsing Singh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structures of RMI1 and RMI2, two OB-fold regulatory subunits of the BLM complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2010.06.008"}], "href": "https://doi.org/10.1016/j.str.2010.06.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20826342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20826342"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Julia A M Bakx, Andreas S Biebricher, Graeme A King, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Duplex DNA and BLM regulate gate opening by the human TopoIIIα-RMI1-RMI2 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-022-28082-5"}], "href": "https://doi.org/10.1038/s41467-022-28082-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35102151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35102151"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Gábor M Harami, János Pálinkás, Yeonee Seol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom's syndrome helicase for efficient disruption of D-loops."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-022-28208-9"}], "href": "https://doi.org/10.1038/s41467-022-28208-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35115525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35115525"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jessica A Kennedy, Salahuddin Syed, Kristina H Schmidt "}, {"type": "b", "children": [{"type": "t", "text": "Structural Motifs Critical for In Vivo Function and Stability of the RecQ-Mediated Genome Instability Protein Rmi1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0145466"}], "href": "https://doi.org/10.1371/journal.pone.0145466"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26717309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26717309"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Michael M Soniat, Giaochau Nguyen, Hung-Che Kuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The MRN complex and topoisomerase IIIa-RMI1/2 synchronize DNA resection motor proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2022.102802"}], "href": "https://doi.org/10.1016/j.jbc.2022.102802"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36529288"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36529288"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "James M Daley, Tamara Chiba, Xiaoyu Xue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multifaceted role of the Topo IIIα-RMI1-RMI2 complex and DNA2 in the BLM-dependent pathway of DNA break end resection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gku803"}], "href": "https://doi.org/10.1093/nar/gku803"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25200081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25200081"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Chang Xu, Lianying Fang, Yangyang Kong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of RMI1 impairs DNA repair under DNA replication stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.10.062"}], "href": "https://doi.org/10.1016/j.bbrc.2017.10.062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29042194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29042194"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Lianying Fang, Xiaohui Sun, Yan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RMI1 contributes to DNA repair and to the tolerance to camptothecin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201802014R"}], "href": "https://doi.org/10.1096/fj.201802014R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30676768"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30676768"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Shimin Chen, Wenbo Liu, Yu Huang "}, {"type": "b", "children": [{"type": "t", "text": "Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-86504-8"}], "href": "https://doi.org/10.1038/s41598-021-86504-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33785812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33785812"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Yuxiao Sun, Lianying Fang, Mengmeng Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and Bioinformatic Assessment of circRNA Expression After "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "RMI1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Knockdown and Ionizing Radiation Exposure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Cell Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/dna.2020.5976"}], "href": "https://doi.org/10.1089/dna.2020.5976"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33202158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33202158"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Manuel Luedeke, Carmen M Linnert, Matthias D Hofer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Predisposition for TMPRSS2-ERG fusion in prostate cancer by variants in DNA repair genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Epidemiol Biomarkers Prev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1055-9965.EPI-09-0772"}], "href": "https://doi.org/10.1158/1055-9965.EPI-09-0772"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19861517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19861517"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Karin Broberg, Elizabeth Huynh, Karin Schläwicke Engström, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-9-140"}], "href": "https://doi.org/10.1186/1471-2407-9-140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19432957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19432957"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Bernd Frank, Michael Hoffmeister, Norman Klopp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Colorectal cancer and polymorphisms in DNA repair genes WRN, RMI1 and BLM."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgp293"}], "href": "https://doi.org/10.1093/carcin/bgp293"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19945966"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19945966"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Jay Yang, Lara O'Donnell, Daniel Durocher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RMI1 promotes DNA replication fork progression and recovery from replication fork stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00255-12"}], "href": "https://doi.org/10.1128/MCB.00255-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22645306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22645306"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Karin Broberg, Mattias Höglund, Cecilia Gustafsson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variant of the human homologous recombination-associated gene RMI1 (S455N) impacts the risk of AML/MDS and malignant melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2007.08.005"}], "href": "https://doi.org/10.1016/j.canlet.2007.08.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17900800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17900800"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Chang Xu, Yan Wang, Lu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Accumulation and Phosphorylation of RecQ-Mediated Genome Instability Protein 1 (RMI1) at Serine 284 and Serine 292 during Mitosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms161125965"}], "href": "https://doi.org/10.3390/ijms161125965"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26556339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26556339"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Arun Pradhan, Thiyam Ramsing Singh, Abdullah Mahmood Ali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Monopolar spindle 1 (MPS1) protein-dependent phosphorylation of RecQ-mediated genome instability protein 2 (RMI2) at serine 112 is essential for BLM-Topo III α-RMI1-RMI2 (BTR) protein complex function upon spindle assembly checkpoint (SAC) activation during mitosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.470823"}], "href": "https://doi.org/10.1074/jbc.M113.470823"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24108125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24108125"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Ipek Ilgin Gönenc, Nursel H Elcioglu, Carolina Martinez Grijalva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phenotypic spectrum of BLM- and RMI1-related Bloom syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.14125"}], "href": "https://doi.org/10.1111/cge.14125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35218564"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35218564"}]}]}]}