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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 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 multi-protein 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)''. The Fanconi Anemia (FA) DNA repair pathway is essential for the recognition and repair of DNA interstrand crosslinks (ICL). A critical step in the pathway is the monoubiquitination of FANCD2 by the RING E3 ligase FANCL. FANCL comprises 3 domains, a RING domain that interacts with E2 conjugating enzyme ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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, FANCG, and FANCL. 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 B. Alternative splicing results in two transcript variants encoding the same protein. Gene FANCB is the only gene known to cause X-linked 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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 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. Mutations involving the FANCA gene are associated with many somatic and congenital defects, primarily involving phenotypic variations of Fanconi anaemia, aplastic anaemia, and forms of cancer such as squamous cell carcinoma and acute myeloid leukaemia. Function The Fanconi anaemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, and FAN ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fanconi Anemia
Fanconi anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. 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), and 90% develop aplastic anemia (the inability to produce blood cells) 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. FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair via homologous recombination. Treatment with androgens and hematopoietic (blood cell) growth factors can help bone marrow failure temporarily, but the long-term treatment is bone marrow ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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, FANCG, FANCI , FANCJ, FANCL, FANCM, FANCN and FANCO. Function Fanconi anemia is a disorder with a recessive Mendelian pattern of inheritance characterized by chromosomal 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 D2. This protein is monoubiquitinated in response to DNA damage, resulting in its localization to nuclear foci with other proteins (BRCA1 and BRCA2) involved in homology-directed DNA repair (see Figure: Recombinational repair of DNA doub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FANCG
Fanconi anemia group G protein is a protein that in humans is encoded by the ''FANCG'' gene. Function 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. 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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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, 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. A nuclear complex containing FANCE protein (as well as FANCC, FANCF and FANCG) is essential for the activation of the FANCD2 protein to the mono-ubiquitinated isoform. In normal, non-mutant cells, FANCD2 is mono-ubiquinated in response to DNA damage. FANCE together with FANCC acts as the su ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ionizing Radiation
Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel up to 99% of the speed of light, and the electromagnetic waves are on the high-energy portion of the electromagnetic spectrum. Gamma rays, X-rays, and the higher energy ultraviolet part of the electromagnetic spectrum are ionizing radiation, whereas the lower energy ultraviolet, visible light, nearly all types of laser light, infrared, microwaves, and radio waves are non-ionizing radiation. The boundary between ionizing and non-ionizing radiation in the ultraviolet area is not sharply defined, as different molecules and atoms ionize at different energies. The energy of ionizing radiation starts between 10 electronvolts (eV) and 33 eV. Typical ionizing subatomic particles include alpha particles, beta particles, and neutrons. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A. The addition of ubiquitin to a substrate protein is called ubiquitylation (or, alternatively, ubiquitination or ubiquitinylation). Ubiquitylation affects proteins in many ways: it can mark them for degradation via the proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions. Ubiquitylation involves three main steps: activation, conjugation, and ligation, performed by ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s), respectively. The result of this sequential cascade is to bind ubiquitin to lysine residues on the protein substrate via an isopeptide bond, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FANCM
Fanconi anemia, complementation group M, also known as FANCM is a human gene. It is an emerging target in cancer therapy, in particular cancers with specific genetic deficiencies. Function The protein encoded by this gene, FANCM displays DNA binding against fork structures and an ATPase activity associated with DNA branch migration. It is believed that FANCM in conjunction with other Fanconi anemia- proteins repair DNA at stalled replication forks, and stalled transcription structures called R-loops. The structure of the C-terminus of FANCM (amino acids 1799-2048), bound to a partner protein FAAP24, reveals how the protein complex recognises branched DNA. A structure of amino acids 675-790 of FANCM reveal how the protein binds duplex DNA through a remodeling of the MHF1:MHF2 histone-like protein complex. Disease association Bi-allelic mutations in the FANCM gene were originally associated with Fanconi anemia, although several individuals with FANCM deficiency do not appear to ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 protein that plays a key role in the proper assembly of the FA core complex. The FA core complex is composed of eight proteins (FANCA, -B, -C, -E, -F, -G, -L and -M). FANCF stabilizes the interaction between the FANCC/FANCE subcomplex and the FANCA/FANCG subcomplex and locks the whole FA core complex in a conformation that is essential to perform its function in DNA repair. The FA core complex is a nuclear core complex that is essential for the monoubiquitination of FANCD2 and this modified form of FANCD2 colocalizes with BRCA1, RAD51 and PCNA in foci that also contain other DNA repair proteins. All these proteins function together to facilitate DNA interstrand cross-link repair. They also function in other DNA damage response repair proce ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fanconi Anemia, Complementation Group C
Fanconi anemia group C protein is a protein that in humans is encoded by the ''FANCC'' gene. Structure Function The protein encoded by this gene delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA. Mutations in this gene result in Fanconi anemia. A nuclear complex containing FANCC protein (as well as FANCA, FANCF and FANCG) is essential for the activation of the FANCD2 protein to the mono-ubiquitinated isoform. In normal, non-mutant, cells FANCD2 is mono-ubiquinated in response to DNA damage. FANCC together with FANCE acts as the substrate adaptor for this reaction Activated FANCD2 protein co-localizes with BRCA1 (breast cancer susceptibility protein) at ionizing radiation-induced foci and in synaptonemal complexes of meiotic chromosomes. Activated FANCD2 protein may function prior to the initiation of meiotic recombination, perhaps to prepare chromosomes for synapsis, or to regulate subsequent recombination events. FANCC(-/-) m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction ra ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
