Langbahn Team – Weltmeisterschaft

FANCI

This article is about a human gene. For the military of Côte d'Ivoire, see National Armed Forces of Côte d'Ivoire.
FANCI
Identifiers
AliasesFANCI, KIAA1794, Fanconi anemia complementation group I, FA complementation group I
External IDsOMIM: 611360; MGI: 2384790; HomoloGene: 49530; GeneCards: FANCI; OMA:FANCI - orthologs
Orthologs
SpeciesHumanMouse
Entrez

55215

208836

Ensembl

ENSG00000140525

ENSMUSG00000039187

UniProt

Q9NVI1

Q8K368

RefSeq (mRNA)

NM_001113378
NM_018193
NM_001376910
NM_001376911

NM_145946

RefSeq (protein)

NP_001106849
NP_060663
NP_001363839
NP_001363840

NP_666058

Location (UCSC)Chr 15: 89.24 – 89.32 MbChr 7: 79.04 – 79.1 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Fanconi anemia, complementation group I (FANCI) also known as KIAA1794, is a protein which in humans is encoded by the FANCI gene.[5][6][7][8][9] Mutations in the FANCI gene are known to cause Fanconi anemia.[10]

Function

The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group I. Alternative splicing results in two transcript variants encoding different isoforms.[5]

FANCI forms a heterodimer with FANCD2 protein. Both FANCD2 and FANCI are monoubiquitinated by the Fanconi anemia core complex subunit FANCL. FANCI monoubiquitination is essential for repairing DNA interstrand crosslinks, and clamps the protein on DNA together with its partner protein FANCD2. The monoubiquitinated FANCD2:FANCI complex coats DNA in a filament-like array, potentially as a way to protect DNA associated with stalled replication.[11]

In addition to proteins involved in DNA repair, FANCI interacts with proteins localized to the nucleolus,[12][13] the nuclear body where ribosome biogenesis initiates. FANCI functions in the processing of the pre-ribosomal RNA (pre-rRNA) for the large ribosomal subunit, the transcription of pre-rRNA by RNAPI, maintaining levels of the mature 28S ribosomal RNA (rRNA), and the global cellular translation of proteins by ribosomes.[12] In the nucleolus, FANCI is predominantly in the deubiquitinated form and interacts with the large subunit of RNAPI and members of the PeBoW complex (PES1 and BOP1).[12] There may be another role for FA proteins outside the nucleolus in ribosome biogenesis or protein translation as FANCI and FANCD2 are the only FA proteins associated with polysomes.[14]

Meiosis

In mice, FANCI protein participates in meiotic recombination of germ cells, and deletion of the Fanci gene causes a strong meiotic phenotype and severe hypogonadism.[15] Fanci-/- male mice have completely impaired spermatogenesis,[15][16] and female Fanci-/- mice produce no ovarian follicles.[15]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000140525 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039187 – 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. ^ a b "Entrez Gene: FANCI".
  6. ^ Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (April 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 8 (2): 85–95. doi:10.1093/dnares/8.2.85. PMID 11347906.
  7. ^ Dorsman JC, Levitus M, Rockx D, Rooimans MA, Oostra AB, Haitjema A, et al. (2007). "Identification of the Fanconi anemia complementation group I gene, FANCI". Cellular Oncology. 29 (3): 211–218. doi:10.1155/2007/151968. PMC 4618213. PMID 17452773.
  8. ^ Sims AE, Spiteri E, Sims RJ, Arita AG, Lach FP, Landers T, et al. (June 2007). "FANCI is a second monoubiquitinated member of the Fanconi anemia pathway". Nature Structural & Molecular Biology. 14 (6): 564–567. doi:10.1038/nsmb1252. PMID 17460694. S2CID 40947913.
  9. ^ Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald ER, Hurov KE, Luo J, et al. (April 2007). "Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair". Cell. 129 (2): 289–301. doi:10.1016/j.cell.2007.03.009. PMC 2175179. PMID 17412408.
  10. ^ Levitus M, Rooimans MA, Steltenpool J, Cool NF, Oostra AB, Mathew CG, et al. (April 2004). "Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes". Blood. 103 (7): 2498–2503. doi:10.1182/blood-2003-08-2915. PMID 14630800. S2CID 7033645.
  11. ^ Tan W, van Twest S, Leis A, Bythell-Douglas R, Murphy VJ, Sharp M, et al. (March 2020). "Monoubiquitination by the human Fanconi anemia core complex clamps FANCI:FANCD2 on DNA in filamentous arrays". eLife. 9. doi:10.7554/eLife.54128. PMC 7156235. PMID 32167469.
  12. ^ a b c Sondalle SB, Longerich S, Ogawa LM, Sung P, Baserga SJ (February 2019). "Fanconi anemia protein FANCI functions in ribosome biogenesis". Proceedings of the National Academy of Sciences of the United States of America. 116 (7): 2561–2570. Bibcode:2019PNAS..116.2561S. doi:10.1073/pnas.1811557116. PMC 6377447. PMID 30692263.
  13. ^ Moriel-Carretero M, Ovejero S, Gérus-Durand M, Vryzas D, Constantinou A (December 2017). "Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors". The Journal of Cell Biology. 216 (12): 4007–4026. doi:10.1083/jcb.201702136. PMC 5716273. PMID 29030393.
  14. ^ Gueiderikh A, Maczkowiak-Chartois F, Rouvet G, Souquère-Besse S, Apcher S, Diaz JJ, Rosselli F (January 2021). "Fanconi anemia A protein participates in nucleolar homeostasis maintenance and ribosome biogenesis". Science Advances. 7 (1): eabb5414. Bibcode:2021SciA....7.5414G. doi:10.1126/sciadv.abb5414. PMC 7775781. PMID 33523834.
  15. ^ a b c Dubois EL, Guitton-Sert L, Béliveau M, Parmar K, Chagraoui J, Vignard J, et al. (August 2019). "A Fanci knockout mouse model reveals common and distinct functions for FANCI and FANCD2". Nucleic Acids Research. 47 (14): 7532–7547. doi:10.1093/nar/gkz514. PMC 6698648. PMID 31219578.
  16. ^ Xu L, Xu W, Li D, Yu X, Gao F, Qin Y, et al. (August 2021). "FANCI plays an essential role in spermatogenesis and regulates meiotic histone methylation". Cell Death & Disease. 12 (8): 780. doi:10.1038/s41419-021-04034-7. PMC 8353022. PMID 34373449. (Erratum: doi:10.1038/s41419-021-04096-7)

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Quelle: http://en.wikipedia.org/wiki/FANCI