| FANCG | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | FANCG , FAG, XRCC9, Fanconi anemia complementation group G, FA complementation group G | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 602956 MGI: 1926471 HomoloGene: 3402 GeneCards: FANCG | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Fanconi anemia group G protein is a protein that in humans is encoded by the FANCG gene. [5] [6] [7]
FANCG, involved in Fanconi anemia, confers resistance to both hygromycin B and mitomycin C. FANCG contains a 5-prime GC-rich untranslated region characteristic of housekeeping genes. The putative 622-amino acid protein has a leucine-zipper motif at its N-terminus. Fanconi anemia is an autosomal recessive disorder with diverse clinical symptoms, including developmental anomalies, bone marrow failure, and early occurrence of malignancies. A minimum of 8 FA genes have been identified. The FANCG gene is responsible for complementation group G. [7]
The clinical phenotype of all Fanconi anemia (FA) complementation groups is similar. This phenotype is characterized by progressive bone marrow failure, cancer proneness and typical birth defects. The main cellular phenotype is hypersensitivity to DNA damage, particularly inter-strand DNA crosslinks. The FA proteins interact through a multiprotein pathway. DNA interstrand crosslinks are highly deleterious damages that are repaired by homologous recombination involving coordination of FA proteins and breast cancer susceptibility gene 1 (BRCA1), but the exact biochemical roles of these proteins is currently unclear.
A nuclear complex containing FANCG (as well as FANCA, FANCB, FANCC, FANCE, FANCF, FANCL and FANCM) is essential for the activation of the FANCD2 protein to the mono-ubiquitinated isoform. [8] In normal, non-mutant, cells FANCD2 is mono-ubiquinated in response to DNA damage. Activated FANCD2 protein co-localizes with BRCA1 (breast cancer susceptibility protein) at ionizing radiation-induced foci and in synaptonemal complexes of meiotic chromosomes (see Figure: Recombinational repair of double strand damage).
Activated FANCD2 protein may function prior to the initiation of meiotic recombination, perhaps to prepare chromosomes for synapsis, or to regulate subsequent recombination events. [15]
Male and female FANCG mutant mice have defective gametogenesis, hypogonadism and impaired fertility, consistent with the phenotype of FA patients. [16] [17] In the non-mutant mouse, FANCG protein is expressed in spermatogonia, preleptotene spermatocytes and spermatocytes in the leptotene, zygotene and early pachytene stages of meiosis. [18]
Loss of FANCG causes neural progenitor apoptosis during forebrain development, likely related to defective DNA repair. [19] (Sii-Felice et al., 2008). This effect persists in adulthood leading to depletion of the neural stem cell pool with aging. The FA phenotype can be interpreted as a premature aging of stem cells, DNA damages being the driving force of aging. [19] (Also see DNA damage theory of aging).
FANCG has been shown to interact with FANCF, [20] [21] [22] [23]
FANCA, [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] FANCE [23] [37] [40] and BRCA2. [41]
Fanconi anemia (FA) is a rare, AR, genetic disease resulting in impaired response to DNA damage in the FA/BRCA pathway. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), MDS, and liver tumors. 90% develop aplastic anemia by age 40. About 60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity. 60% of FA is FANC-A, 16q24.3, which has later onset bone marrow failure.
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in the budding yeast S. cerevisiae, and the fission yeast S. pombe, where it is encoded by genes cdc28 and cdc2, respectively. With its cyclin partners, Cdk1 forms complexes that phosphorylate a variety of target substrates ; phosphorylation of these proteins leads to cell cycle progression.
Glutathione S-transferase P is an enzyme that in humans is encoded by the GSTP1 gene.
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, a human rare disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages.
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 complementation groups are currently recognized and is hypothesised to operate as a post-replication repair or a cell cycle checkpoint. FANCA proteins are involved in inter-strand DNA cross-link repair and in the maintenance of normal chromosome stability that regulates the differentiation of haematopoietic stem cells into mature blood cells.
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, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN and FANCO.
Fanconi anemia group F protein is a protein that in humans is encoded by the FANCF gene.
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, FANCD2, FANCE, FANCF, FANCG, and FANCL. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA cross-linking 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 groufcrp E.
E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the FANCL gene.
Fanconi anemia group B protein is a protein that in humans is encoded by the FANCB gene.
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.
T-complex protein 1 subunit gamma is a protein that in humans is encoded by the CCT3 gene.
Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the PALB2 gene.
Zinc finger and BTB domain-containing protein 32 is a protein that in humans is encoded by the 1960 bp ZBTB32 gene. The 52 kDa protein is a transcriptional repressor and the gene is expressed in T and B cells upon activation, but also significantly in testis cells. It is a member of the Poxviruses and Zinc-finger (POZ) and Krüppel (POK) family of proteins, and was identified in multiple screens involving either immune cell tumorigenesis or immune cell development.
Ubiquitin-specific protease 14 is an enzyme that in humans is encoded by the USP14 gene.
RecQ-mediated genome instability protein 1 is a protein that in humans is encoded by the RMI1 gene.
FANC proteins are a network of at least 15 proteins that are associated with a cell process known as the Fanconi anemia.
Alan D. D'Andrea is an American cancer researcher and the Fuller American Cancer Society Professor of Radiation Oncology at Harvard Medical School. D'Andrea's research at the Dana Farber Cancer Institute focuses on chromosome instability and cancer susceptibility. He is currently the director of the Center for DNA Damage and Repair and the director of the Susan F. Smith Center for Women's Cancer.
FANCD2/FANCI-associated nuclease 1 (KIAA1018) is an enzyme that in humans is encoded by the FAN1 gene. It is a structure dependent endonuclease. It is thought to play an important role in the Fanconi Anemia (FA) pathway.
Ketan Jayakrishna Patel is a British-Kenyan scientist who is Director of the MRC Weatherall Institute of Molecular Medicine and the MRC Molecular Haematology Unit at the University of Oxford. Until 2020 he was a tenured principal investigator at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB).
| Excision repair | |
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| Other forms of repair | |
| Other/ungrouped proteins | |
| Regulation | |
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