Last update 19 Sep 2024

RMI1

Last update 19 Sep 2024

Basic Info

Synonyms

BLAP75, BLM-associated protein of 75 kDa, C9orf76

+ [5]

Introduction

Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability.

Drugs associated with RMI1

PIP-199

Target

FANCM x RMI1 x RMI2

Mechanism

FANCM inhibitors [+2]

Active Org.

The University of Sydney

Originator Org.

The University of Sydney

Active Indication

Bloom Syndrome [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with RMI1

100 Translational Medicine associated with RMI1

0 Patents (Medical) associated with RMI1

150

Literatures (Medical) associated with RMI1

15 Apr 2024·Clinical Cancer Research

Germline Mutations of Holliday Junction Resolvase Genes in Multiple Primary Malignancies Involving Lung Cancer Lead to PARP Inhibitor Sensitization

Article

Author: Chen, Yuping ; Zhang, Jie ; Yang, Jie ; Xie, Juntao ; Wang, Haoran ; Huang, Binhao ; Yuan, Jian ; Wang, Xinshu ; Yin, Hui ; Wu, Jinhuan

AbstractPurpose:The incidence of multiple primary malignancies (MPM) involving lung cancer has increased in recent decades. There is an urgent need to clarify the genetic profile of such patients and explore more efficacious therapy for them.Experimental Design:Peripheral blood samples from MPM involving patients with lung cancer were assessed by whole-exome sequencing (WES), and the identified variants were referenced for pathogenicity using the public available database. Pathway enrichment analysis of mutated genes was performed to identify the most relevant pathway. Next, the effects of mutations in relevant pathway on function and response to targeted drugs were verified by in vitro and in vivo experiments.Results:Germline exomes of 71 patients diagnosed with MPM involving lung cancer were sequenced. Pathway enrichment analysis shows that the homologous recombination repair (HRR) pathway has the strongest correlation. Moreover, HRR genes, especially key Holliday junction resolvases (HJR) genes (GEN1, BLM, SXL4, and RMI1), were most frequently mutated, unlike the status in the samples from patients with lung cancer only. Next, we identified a total of seven mutations in HJR genes led to homologous recombination DNA repair deficiency and rendered lung cancer cells sensitive to PARP inhibitor treatment, both in vitro and in vivo.Conclusions:This is the first study to map the profile of germline mutations in patients with MPM involving lung cancer. This study may shed light on early prevention and novel targeted therapies for MPM involving patients with lung cancer with HJR mutations.

01 Apr 2024·The Journal of Obstetrics and Gynecology of India

Comparison of Simple Ultrasound Rules by International Ovarian Tumor Analysis (IOTA) with RMI-1 and RMI-4 (Risk of Malignancy Index) in Preoperative Differentiation of Benign and Malignant Adnexal Masses

Article

Author: Dewangan, Shalinee ; Gupta, Sonal ; Chawla, Indu

BackgroundIOTA proposed Simple Ultrasound Rules in 2009 for preoperative diagnosis of ovarian masses based on ultrasound only. It is an accurate, simple and inexpensive method. RMI, however, requires CA125 level. While RMI-4 is the latest, RMI-1 is still the most widely used method. The present study was done to compare IOTA Rules with RMI-1 and RMI-4.PurposeTo differentiate benign and malignant adnexal masses preoperatively using IOTA simple rules and compare its accuracy with RMI-1 and RMI-4.MethodsA prospective observational study was performed from 1st November 2019 to 31st March 2021 in the Department of Obstetrics and Gynaecology, ABVIMS and Dr. RML Hospital, New Delhi. This study was conducted on 70 patients with adnexal masses who underwent pre-operative evaluation using IOTA Simple Rules, RMI-1 and RMI-4. Histopathology was used to compare the results.ResultsOut of 70 patients, 59 (84.3%) cases were benign and 11 (15.7%) were malignant. The IOTA Rules were applicable to 60 cases (85.7%), and the results were inconclusive in 10 cases (14.3%). Where applicable, the sensitivity and specificity of the IOTA Rules (88.9% and 94.1%, respectively) were significantly higher than RMI-1 (45.5% and 93.2%, respectively) and RMI-4 (45.5% and 89.8%, respectively). When inconclusive results were included as malignant, the sensitivity of the IOTA Rules increased (88.9% vs 90.9%); however, the specificity decreased (94.1% vs 81.4%).ConclusionIOTA Simple Rules were more accurate at diagnosing benign from malignant adnexal masses than RMI-1 and RMI-4. However, the rules were not applicable to 14% of the cases.

01 Feb 2024·Molecular Cell

BLM and BRCA1-BARD1 coordinate complementary mechanisms of joint DNA molecule resolution

Article

Author: Bannister, Julius ; Jones, Samuel E ; Tsukada, Kaima ; Fawkes, Matthew ; Blackford, Andrew N ; Kessler, Benedikt M ; Fischer, Roman ; Vendrell, Iolanda ; Chapman, J Ross ; Durin, Mary-Anne

The Bloom syndrome helicase BLM interacts with topoisomerase IIIα (TOP3A), RMI1, and RMI2 to form the BTR complex, which dissolves double Holliday junctions and DNA replication intermediates to promote sister chromatid disjunction before cell division. In its absence, structure-specific nucleases like the SMX complex (comprising SLX1-SLX4, MUS81-EME1, and XPF-ERCC1) can cleave joint DNA molecules instead, but cells deficient in both BTR and SMX are not viable. Here, we identify a negative genetic interaction between BLM loss and deficiency in the BRCA1-BARD1 tumor suppressor complex. We show that this is due to a previously overlooked role for BARD1 in recruiting SLX4 to resolve DNA intermediates left unprocessed by BLM in the preceding interphase. Consequently, cells with defective BLM and BRCA1-BARD1 accumulate catastrophic levels of chromosome breakage and micronucleation, leading to cell death. Thus, we reveal mechanistic insights into SLX4 recruitment to DNA lesions, with potential clinical implications for treating BRCA1-deficient tumors.

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RMI1

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