Fanconi anemia group B protein 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 ...

that in humans is encoded by the ''FANCB''

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 ...

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,

FANCC Fanconi anemia group C protein is a protein that in humans is encoded by the ''FANCC'' gene. This protein delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA. Mutations in this gene result in Fanconi anemia, ...

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 Fanconi anemia group D2 protein is a protein that in humans is encoded by the ''FANCD2'' gene. The Fanconi anemia complementation group ( FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2 (this gene), FANCE, FANCF ...

FANCE Fanconi anemia, complementation group E protein is a protein that in humans is encoded by the ''FANCE'' gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANC ...

FANCF Fanconi anemia group F protein is a protein that in humans is encoded by the ''FANCF'' gene. Interactions FANCF has been shown to interact with Fanconi anemia, complementation group C, FANCG, FANCA and FANCE. Function FANCF is an adaptor ...

, FANCG, and

FANCL E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the ''FANCL'' gene. Function The clinical phenotype of mutational defects in all Fanconi anemia (FA) complementation groups is similar. This phenotype is characteri ...

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 DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...

. 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 B. Alternative splicing results in two transcript variants encoding the same protein.

Gene

FANCB is the only gene known to cause

X-linked Sex linkage describes the sex-specific patterns of inheritance and expression when a gene is present on a sex chromosome (allosome) rather than a non-sex chromosome ( autosome). Genes situated on the X-chromosome are thus termed X-linked, and ...

Fanconi Anemia. In female carriers of FANCB mutations (one wild-type FANCB allele and one mutant FANCB allele) there is strong selection through

X-inactivation X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into ...

for expression of only the wild-type allele. In contrast, males have only one FANCB allele. Only male patients with Fanconi anemia have ever been linked to FANCB mutations, and they make up about 4% of cases. Mutation in the FANCB are highly associated with the development of the VACTERL-H constilation of birth defects. In a cohort study of 19 children with FANCB variants, those with deletion of FANCB gene or truncation of FANCB protein demonstrate earlier-than-average onset of bone marrow failure and more severe congenital abnormalities compared with a large series of Fanconi Anemia individuals in published reports. This reflects the indispensable role of FANCB gene in cells. For FANCB missense variants, more variable severity is associated with the extent of residual activity.

Protein

The ''FANCB'' gene product is FANCB protein. FANCB is a component of a "core complex" of nine Fanconi Anemia proteins:

, FANCB,

, FANCG,

, FAAP100 and FAAP20. The core complex localises to DNA damage sites during

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...

where it catalyzes transfer of

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...

and

FANCI Fanconi anemia, complementation group I (FANCI) also known as KIAA1794, is a protein which in humans is encoded by the ''FANCI'' gene. Mutations in the ''FANCI'' gene are known to cause Fanconi anemia. Function The Fanconi anemia complementa ...

. In particular, this reaction is necessary for the repair of DNA interstrand crosslinks, such as those formed by chemotherapy drugs

cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...

mitomycin c Mitomycin C is a mitomycin that is used as a chemotherapy, chemotherapeutic agent by virtue of its antitumour activity. Medical uses It is given intravenously to treat upper gastro-intestinal cancers (e.g. esophageal carcinoma), anal cancer ...

and

melphalan Melphalan, sold under the brand name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma; malignant lymphoma; lymphoblastic and myeloblastic leukemia; childhood neuroblastoma; ovarian cancer; mammary adenocar ...

. Within the Fanconi anemia core complex, FANCB has an obligate interaction with FAAP100 and FANCL, to form a catalytic E3 RING ligase enzyme. FANCB creates a dimer interface within this subcomplex that is required for simultaneous ubiquitination of FANCD2 and FANCI. Electron microscopy imaging of the FANCB-FANCL-FAAP100 complex revealed a symmetry that is centred on FANCB, and biochemical investigation confirmed that the entire complex is a dimer containing two of each subunit. Further imaging reveals the overall architecture of the Fanconi Anemia core complex centres on FANCB protein.

Meiosis

FANCB mutant mice are

infertile In biology, infertility is the inability of a male and female organism to reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, which is the body's sta ...

and exhibit primordial

germ cell A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they unde ...

defects during

embryogenesis An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...

. The germ cells and

testicular A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone. The r ...

size are severely compromised in FANCB mutant mice. FANCB protein is essential for

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 likely has a role in the activation of the Fanconi anemia DNA repair pathway during

meiosis 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 c ...

References

External links

{{DNA repair Human proteins