Fanconi anemia, complementation group I (FANCI) also known as KIAA1794, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
which in humans is encoded by the ''FANCI''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Mutations in the ''FANCI'' gene are known to cause
Fanconi anemia
Fanconi anemia (FA) is a rare, autosomal recessive genetic disease characterized by aplastic anemia, congenital defects, endocrinological abnormalities, and an increased incidence of developing cancer. The study of Fanconi anemia has improve ...
.
Function
The Fanconi anemia complementation group (FANC) currently includes
FANCA
Fanconi anaemia, complementation group A, also known as FAA, FACA and FANCA, is a protein which in humans is encoded by the ''FANCA'' gene. It belongs to the Fanconi anaemia complementation group (FANC) family of genes of which 12 complementatio ...
,
FANCB
Fanconi anemia group B protein is a protein that in humans is encoded by the ''FANCB'' gene.
Function
The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FAN ...
,
FANCC,
FANCD1
''BRCA2'' and BRCA2 () are human genes and their protein products, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associate ...
(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
Fanconi anemia (FA) is a rare, autosomal recessive genetic disease characterized by aplastic anemia, congenital defects, endocrinological abnormalities, and an increased incidence of developing cancer. The study of Fanconi anemia has improve ...
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.
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.
In addition to proteins involved in DNA repair, FANCI interacts with proteins localized to the
nucleolus
The nucleolus (; : nucleoli ) is the largest structure in the cell nucleus, nucleus of eukaryote, eukaryotic cell (biology), cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signa ...
,
the
nuclear body where
ribosome biogenesis
Ribosome biogenesis is the process of making ribosomes. In prokaryotes, this process takes place in the cytoplasm with the transcription of many ribosome gene operons. In eukaryotes, it takes place both in the cytoplasm and in the nucleolus. ...
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
Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...
of proteins by
ribosomes
Ribosomes () are macromolecular machines, found within all cells, that perform biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to fo ...
.
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
Ribosome biogenesis protein BOP1 is a protein that in humans is encoded by the ''BOP1'' gene. It is a WD40 repeat-containing nucleolar protein involved in rRNA processing, thereby controlling the cell cycle. It is required for the maturation o ...
).
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.
Meiosis
In mice, FANCI protein participates in
meiotic
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one copy ...
recombination of germ cells, and deletion of the ''Fanci'' gene causes a strong meiotic phenotype and severe
hypogonadism
Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...
.
''Fanci''-/- male mice have completely impaired
spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...
,
[ ] and female ''Fanci''-/- mice produce no ovarian follicle
An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. In humans, women have approximately 200,000 to 300,000 follicles at the time of puberty, ea ...
s.[
]
References
Further reading
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External links
{{DNA repair
Human proteins