RMI1

RMI1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3MXN, 3NBH, 3NBI, 4CGY, 4CHT, 4DAY
Identifiers
Aliases	RMI1 , BLAP75, C9orf76, FAAP75, RecQ mediated genome instability 1
External IDs	OMIM: 610404; MGI: 1921636; HomoloGene: 41601; GeneCards: RMI1; OMA:RMI1 - orthologs
Gene location (Human) Chr. Chromosome 9 (human) [1] Band 9q21.32 Start 83,980,798 bp [1] End 84,004,074 bp [1]
Gene location (Mouse) Chr. Chromosome 13 (mouse) [2] Band 13|13 B1 Start 58,550,062 bp [2] End 58,558,962 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte Epithelium of choroid plexus gonad bronchial epithelial cell ventricular zone embryo ganglionic eminence testicle retinal pigment epithelium Top expressed in zygote secondary oocyte spermatocyte Rostral migratory stream spermatid genital tubercle tail of embryo hand primary oocyte otolith organ More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding protein binding Cellular component nucleus nucleoplasm nuclear body RecQ family helicase-topoisomerase III complex Biological process DNA replication response to dietary excess reduction of food intake in response to dietary excess response to glucose multicellular organism growth glucose homeostasis resolution of meiotic recombination intermediates double-strand break repair via homologous recombination regulation of signal transduction by p53 class mediator Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 80010 74386 Ensembl ENSG00000178966 ENSMUSG00000035367 UniProt Q9H9A7 Q9D4G9 RefSeq (mRNA) NM_024945 NM_001358291 NM_001358292 NM_001358293 NM_001358294 NM_001168248 NM_028904 RefSeq (protein) NP_079221 NP_001345220 NP_001345221 NP_001345222 NP_001345223 NP_001161720 NP_083180 Location (UCSC) Chr 9: 83.98 – 84 Mb Chr 13: 58.55 – 58.56 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

RecQ-mediated genome instability protein 1 is a protein that in humans is encoded by the RMI1 gene. ^{[5] [6]}

Genetic disorders

Mutations in RMI1 are associated with Bloom-Syndrome like disorder. ^[7] Two patients, both with microcephalic dwarfism came from the same family. They carried identical heterozygous mutations: [1255_1259del][Lys419LeufsTer5].

Function

RMI1 protein is a component of the Bloom Syndrome Complex. ^[8] RMI1 protein is made up of 2 OB (oligonucleotide binding) domains. OB1 binds to Topoisomerase III alpha, ^[9] while OB2 binds to RMI2 within the Bloom Syndrome complex, and FANCM of the Fanconi Anaemia pathway. ^[10]

An insert within OB1 domain of RMI1 inserts into the catalytic centre of Topoisomerase III alpha, and is necessary for the optimal activity of this enzyme during cellular DNA repair and homologous recombination. ^[9]

Meiosis

During meiosis in budding yeast Saccharomyces cerevisiae , TOP3 (a type I topoisomerase) and its accessory factor RMI1 form a heterodimer that functions to allow passage of one DNA single strand through another. The TOP3-RMI1 heterodimer associates with Sgs1 (Bloom helicase ortholog) to form a complex that catalyzes dissolution of double Holliday junctions. ^[11] Furthermore, the TOP3-RMI1 heterodimer participates in all meiotic recombination functions associated with Sgs1, most significantly as an early recombination intermediate chaperone, promoting regulated crossover and non-crossover recombination and preventing accumulation of aberrant recombination intermediates. ^[12] In particular, the TOP3-RMI1–SGS1 complex promotes early formation of non-crossover recombinants during meiosis. ^[12]

References

1. GRCh38: Ensembl release 89: ENSG00000178966 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035367 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Yin J, Sobeck A, Xu C, Meetei AR, Hoatlin M, Li L, Wang W (April 2005). "BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity". The EMBO Journal. 24 (7): 1465–1476. doi:10.1038/sj.emboj.7600622. PMC   1142546 . PMID   15775963.
6. "Entrez Gene: RMI1 RMI1, RecQ mediated genome instability 1, homolog (S. cerevisiae)".
7. Martin CA, Sarlós K, Logan CV, Thakur RS, Parry DA, Bizard AH, et al. (August 2018). "Mutations in TOP3A Cause a Bloom Syndrome-like Disorder". American Journal of Human Genetics. 103 (2): 221–231. doi:10.1016/j.ajhg.2018.07.001. PMC   6080766 . PMID   30057030.
8. Hodson C, Low JK, van Twest S, Jones SE, Swuec P, Murphy V, et al. (February 2022). "Mechanism of Bloom syndrome complex assembly required for double Holliday junction dissolution and genome stability". Proceedings of the National Academy of Sciences of the United States of America. 119 (6): e2109093119. Bibcode:2022PNAS..11909093H. doi: 10.1073/pnas.2109093119 . PMC   8832983 . PMID   35115399.
9. Bocquet N, Bizard AH, Abdulrahman W, Larsen NB, Faty M, Cavadini S, et al. (March 2014). "Structural and mechanistic insight into Holliday-junction dissolution by topoisomerase IIIα and RMI1". Nature Structural & Molecular Biology. 21 (3): 261–268. doi:10.1038/nsmb.2775. PMC   4292918 . PMID   24509834.
10. Deans AJ, West SC (December 2009). "FANCM connects the genome instability disorders Bloom's Syndrome and Fanconi Anemia". Molecular Cell. 36 (6): 943–953. doi: 10.1016/j.molcel.2009.12.006 . PMID   20064461.
11. Bizard AH, Hickson ID (July 2014). "The dissolution of double Holliday junctions". Cold Spring Harbor Perspectives in Biology. 6 (7): a016477. doi:10.1101/cshperspect.a016477. PMC   4067992 . PMID   24984776.
12. Kaur H, De Muyt A, Lichten M (February 2015). "Top3-Rmi1 DNA single-strand decatenase is integral to the formation and resolution of meiotic recombination intermediates". Molecular Cell. 57 (4): 583–594. doi:10.1016/j.molcel.2015.01.020. PMC   4338413 . PMID   25699707.

Further reading

• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, et al. (October 2003). "A novel ubiquitin ligase is deficient in Fanconi anemia". Nature Genetics. 35 (2): 165–170. doi:10.1038/ng1241. PMID   12973351. S2CID   10149290.
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, et al. (September 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research. 14 (9): 1711–1718. doi:10.1101/gr.2435604. PMC   515316 . PMID   15342556.
• Wu L, Bachrati CZ, Ou J, Xu C, Yin J, Chang M, et al. (March 2006). "BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates". Proceedings of the National Academy of Sciences of the United States of America. 103 (11): 4068–4073. Bibcode:2006PNAS..103.4068W. doi: 10.1073/pnas.0508295103 . PMC   1449647 . PMID   16537486.
• Raynard S, Bussen W, Sung P (May 2006). "A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75". The Journal of Biological Chemistry. 281 (20): 13861–13864. doi: 10.1074/jbc.C600051200 . PMID   16595695.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi: 10.1016/j.cell.2006.09.026 . PMID   17081983. S2CID   7827573.
• Bussen W, Raynard S, Busygina V, Singh AK, Sung P (October 2007). "Holliday junction processing activity of the BLM-Topo IIIalpha-BLAP75 complex". The Journal of Biological Chemistry. 282 (43): 31484–31492. doi: 10.1074/jbc.M706116200 . PMID   17728255.
• Broberg K, Höglund M, Gustafsson C, Björk J, Ingvar C, Albin M, Olsson H (December 2007). "Genetic variant of the human homologous recombination-associated gene RMI1 (S455N) impacts the risk of AML/MDS and malignant melanoma". Cancer Letters. 258 (1): 38–44. doi:10.1016/j.canlet.2007.08.005. PMID   17900800.