Biology:FANCI

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Fanconi anemia, complementation group I (FANCI) also known as KIAA1794, is a protein which in humans is encoded by the FANCI gene.[1][2][3][4][5] Mutations in the FANCI gene are known to cause Fanconi anemia.[6]

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.[1]

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.[7]

In addition to proteins involved in DNA repair, FANCI interacts with proteins localized to the nucleolus,[8][9] 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.[8] 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).[8] 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.[10]

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.[11] Fanci-/- male mice have completely impaired spermatogenesis,[11][12] and female Fanci-/- mice produce no ovarian follicles.[11]

References

  1. ↑ 1.0 1.1 "Entrez Gene: FANCI". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55215. 
  2. ↑ "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. April 2001. doi:10.1093/dnares/8.2.85. PMID 11347906. 
  3. ↑ "Identification of the Fanconi anemia complementation group I gene, FANCI". Cellular Oncology 29 (3): 211–218. 2007. doi:10.1155/2007/151968. PMID 17452773. 
  4. ↑ "FANCI is a second monoubiquitinated member of the Fanconi anemia pathway". Nature Structural & Molecular Biology 14 (6): 564–567. June 2007. doi:10.1038/nsmb1252. PMID 17460694. 
  5. ↑ "Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair". Cell 129 (2): 289–301. April 2007. doi:10.1016/j.cell.2007.03.009. PMID 17412408. 
  6. ↑ "Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes". Blood 103 (7): 2498–2503. April 2004. doi:10.1182/blood-2003-08-2915. PMID 14630800. 
  7. ↑ "Monoubiquitination by the human Fanconi anemia core complex clamps FANCI:FANCD2 on DNA in filamentous arrays". eLife 9. March 2020. doi:10.7554/eLife.54128. PMID 32167469. 
  8. ↑ 8.0 8.1 8.2 "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. February 2019. doi:10.1073/pnas.1811557116. PMID 30692263. Bibcode: 2019PNAS..116.2561S. 
  9. ↑ "Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors". The Journal of Cell Biology 216 (12): 4007–4026. December 2017. doi:10.1083/jcb.201702136. PMID 29030393. 
  10. ↑ "Fanconi anemia A protein participates in nucleolar homeostasis maintenance and ribosome biogenesis". Science Advances 7 (1): eabb5414. January 2021. doi:10.1126/sciadv.abb5414. PMID 33523834. Bibcode: 2021SciA....7.5414G. 
  11. ↑ 11.0 11.1 11.2 "A Fanci knockout mouse model reveals common and distinct functions for FANCI and FANCD2". Nucleic Acids Research 47 (14): 7532–7547. August 2019. doi:10.1093/nar/gkz514. PMID 31219578. 
  12. ↑ "FANCI plays an essential role in spermatogenesis and regulates meiotic histone methylation". Cell Death & Disease 12 (8): 780. August 2021. doi:10.1038/s41419-021-04034-7. PMID 34373449.  (Erratum: doi:10.1038/s41419-021-04096-7. If the erratum has been checked and does not affect the cited material, please replace {{Erratum|...}} with {{Erratum|...|checked=yes}}.)

Further reading

External links

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



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