Ataxia telangiectasia mutated
Encyclopedia
Ataxia telangiectasia mutated (ATM) is a serine
/threonine
protein kinase
that is recruited and activated by DNA
double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint
, leading to cell cycle
arrest, DNA repair
or apoptosis
. Several of these targets, including p53
, CHK2 and H2AX are tumor suppressors.
The protein is named for the disorder Ataxia telangiectasia caused by mutations of ATM.
the DNA is monitored for damage. Damages result from errors during replication
, by-products of metabolism, general toxic drugs or ionizing radiation
. The cell cycle has different DNA damage checkpoints, which inhibit or maintain the next cell cycle
step. There are two main checkpoints, the G1/S and the G2/M, during the cell cycle, which preserve correct progression. ATM plays a role in cell cycle delay after DNA damage, especially after double-strand breaks (DSBs). ATM together with NBS1 act as primary DSB sensor proteins. Different mediators, such as Mre11 and MDC1
, acquire post-translational modifications which are generated by the sensor proteins. These modified mediator proteins then amplify the DNA damage signal, and transduce the signals to downstream effectors such as CHK2 and p53
.
s (PIKKs). The PIKK superfamily comprises six Ser/Thr-protein kinases that show a sequence similarity to phosphatidylinositol 3-kinases (PI3Ks). This protein kinase family includes amongst others ATR
(ATM- and RAD3-related), DNA-PKcs (DNA-dependent protein kinase catalytic subunit) and mTOR (mammalian target of rapamycin). Characteristic for ATM are five domains. These are from N-Terminus to C-Terminus the HEAT repeat domain
, the FRAP-ATM-TRRAP (FAT) domain, the kinase domain (KD), the PIKK-regulatory domain (PRD) and the FAT-C-terminal (FATC) domain. The HEAT repeats directly bind to the C-terminus of NBS1. The FAT domain interacts with ATM's kinase domain to stabilize the C-terminus region of ATM itself. The KD domain resumes kinase activity, while the PRD and the FATC domain regulate it. Although no structure for ATM has been solved, the overall shape of ATM is very similar to DNA-PKcs and is composed of a head and a long arm that is thought to wrap around double-stranded DNA after a conformational change. The entire N-terminal domain together with the FAT domain are predicted to adobt an α-helical structure, which was found by sequence analysis. This α-helical structure is believed to form a tertiary structure
, which has a curved, tubular shape present for example in the Huntingtin
protein, which also contains HEAT repeats. FATC is the C-terminal domain with a length of about 30 amino acids. It is highly conserved and consists of an α-helix followed by a sharp turn, which is stabilized by a disulfide bond
.
and NBS1 (XRS
in yeast), called the MRN
complex in humans, recruits ATM to double strand breaks (DSBs) and holds the two ends together. ATM directly interacts with the NBS1 subunit and phosphorylates the histone variant H2AX on Ser139. This phosphorylation generates binding sites for adaptor proteins with a BRCT domain
. These adaptor proteins then recruit different factors including the effector protein kinase CHK2 and the tumor suppressor p53
. The ATM-mediated DNA damage response consists of a rapid and a delayed response. The effector kinase CHK2 is phopsphorylated and thereby activated by ATM. Activated CHK2 phophorylates phosphatase CDC25A
which is degraded thereupon and can no longer dephosphororylate CDK2-Cyclin
resulting in cell-cycle arrest. If the DSB can not be repaired during this rapid response, ATM additionally phophorylates MDM2
and p53
at Ser15. p53 is also phosphorylated by the effector kinase CHK2. These phosphorylation events lead to stabilization and activation of p53
and subsequent transcription of numerous p53
target genes including Cdk inhibitor p21
which lead to long-term cell-cycle arrest or even apoptosis.
.
Inactive ATM is present in the cells without DSBs as dimers or multimers. Upon DNA damage, ATM autophosphorylates on residue Ser1981. This phosphorylation provokes dissociation of ATM dimers, which is followed by the release of active ATM monomers. Further autophosphorylation (of residues Ser367 and Ser1893) is required for normal activity of the ATM kinase. Activation of ATM by the MRN
complex is preceded by at least two steps, i.e. recruitment of ATM to DSB ends by the mediator of DNA damage checkpoint protein 1 (MDC1
) which binds to MRE11, and the subsequent stimulation of kinase activity with the NBS1 C-terminus.
The three domains FAT, PRD and FATC are all involved in regulating the activity of the KD kinase domain. The FAT domain interacts with ATM's KD domain to stabilize the C-terminus region of ATM itself. The FATC domain is critical for kinase activity and highly sensitive to mutagenesis. It mediates protein-protein interaction for example with the histone acetyltransferase
TIP60 (HIV-1 Tat interacting protein 60 kDa), which acetylates ATM on residue Lys3016. The acetylation occurs in the C-terminal half of the PRD domain and is required for ATM kinase activation and for its conversion into monomers. While deletion of the entire PRD domain abolishes the kinase activity of ATM, specific small deletions show no effect.
(AT) is a rare human disease characterized by extreme cellular sensitivity to radiation and a predisposition to cancer. All AT patients contain mutations in the AT-mutated gene (ATM). Most other AT-like disorders are defective in genes encoding the MRN
protein complex. One feature of the ATM protein is its rapid increase in kinase
activity immediately following double-strand break formation. The phenotypic manifestation of AT is due to the broad range of substrates for the ATM kinase, involving DNA repair, apoptosis
, G1/S, intra-S checkpoint and G2/M checkpoints, gene regulation, translation
initiation
, and telomere
maintenance. Therefore a defect in ATM has severe consequences in repairing certain types of damage to DNA, and cancer
may result from improper repair. AT patients have an increased risk for breast cancer that has been ascribed to ATM's interaction and phosphorylation of BRCA1
and its associated proteins following DNA damage. Certain kinds of leukemia
s and lymphoma
s, including Mantle cell lymphoma
, T-ALL, atypical B cell chronic lymphocytic leukemia, and T-PLL are also associated with ATM defects.
with RAD17
, RBBP8
, RAD51
, DNA-PKcs, RRM2B
, FANCD2
, Nibrin
, TERF1
, BRCA1
, Abl gene
, TP53BP1
, MRE11A
, P53
, Bloom syndrome protein
, SMC1A
and RHEB
.
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
/threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
protein kinase
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...
that is recruited and activated by DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint
Cell cycle checkpoint
Cell cycle checkpoints are control mechanisms that ensure the fidelity of cell division in eukaryotic cells. These checkpoints verify whether the processes at each phase of the cell cycle have been accurately completed before progression into the next phase...
, leading to cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
arrest, DNA repair
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
or apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. Several of these targets, including p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, CHK2 and H2AX are tumor suppressors.
The protein is named for the disorder Ataxia telangiectasia caused by mutations of ATM.
Introduction
Throughout the cell cycleCell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
the DNA is monitored for damage. Damages result from errors during replication
Replication
Replication may refer to:Science* Replication is one of the main principles of the scientific method, a.k.a. reproducibility** Replication , the repetition of a test or complete experiment...
, by-products of metabolism, general toxic drugs or ionizing radiation
Ionizing radiation
Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...
. The cell cycle has different DNA damage checkpoints, which inhibit or maintain the next cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
step. There are two main checkpoints, the G1/S and the G2/M, during the cell cycle, which preserve correct progression. ATM plays a role in cell cycle delay after DNA damage, especially after double-strand breaks (DSBs). ATM together with NBS1 act as primary DSB sensor proteins. Different mediators, such as Mre11 and MDC1
MDC1
Mediator of DNA damage checkpoint protein 1 is a protein that in humans is encoded by the MDC1 gene.-Interactions:MDC1 has been shown to interact with MRE11A, H2AFX and CHEK2.-Further reading:...
, acquire post-translational modifications which are generated by the sensor proteins. These modified mediator proteins then amplify the DNA damage signal, and transduce the signals to downstream effectors such as CHK2 and p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
.
Structure
The ATM gene codes for a 350 kDa protein consisting of 3056 amino acids. ATM belongs to the superfamily of Phosphatidylinositol 3-kinase-related kinasePhosphatidylinositol 3-kinase-related kinase
Phosphatidylinositol 3-kinase-related kinases are a family of Ser/Thr-protein kinases with sequence similarity to phosphatidylinositol-3 kinases .- Members :The human PIKK family includes six members:- Structure :...
s (PIKKs). The PIKK superfamily comprises six Ser/Thr-protein kinases that show a sequence similarity to phosphatidylinositol 3-kinases (PI3Ks). This protein kinase family includes amongst others ATR
ATR
ATR is an Italian-French aircraft manufacturer headquartered on the grounds of Toulouse Blagnac International Airport in Blagnac, France surburb of Toulouse. It was formed in 1981 by Aérospatiale of France and Aeritalia of Italy...
(ATM- and RAD3-related), DNA-PKcs (DNA-dependent protein kinase catalytic subunit) and mTOR (mammalian target of rapamycin). Characteristic for ATM are five domains. These are from N-Terminus to C-Terminus the HEAT repeat domain
Heat repeat domain
The HEAT repeat domain is a protein domain found in a number of cytoplasmic proteins including the four that the give rise to the acronym HEAT . HEAT repeats form a rod-like helical structures which are involved in intracellular transport....
, the FRAP-ATM-TRRAP (FAT) domain, the kinase domain (KD), the PIKK-regulatory domain (PRD) and the FAT-C-terminal (FATC) domain. The HEAT repeats directly bind to the C-terminus of NBS1. The FAT domain interacts with ATM's kinase domain to stabilize the C-terminus region of ATM itself. The KD domain resumes kinase activity, while the PRD and the FATC domain regulate it. Although no structure for ATM has been solved, the overall shape of ATM is very similar to DNA-PKcs and is composed of a head and a long arm that is thought to wrap around double-stranded DNA after a conformational change. The entire N-terminal domain together with the FAT domain are predicted to adobt an α-helical structure, which was found by sequence analysis. This α-helical structure is believed to form a tertiary structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
, which has a curved, tubular shape present for example in the Huntingtin
Huntingtin
The Huntingtin gene, also called HTT or HD gene, is the IT15 gene which codes for a protein called the huntingtin protein...
protein, which also contains HEAT repeats. FATC is the C-terminal domain with a length of about 30 amino acids. It is highly conserved and consists of an α-helix followed by a sharp turn, which is stabilized by a disulfide bond
Disulfide bond
In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...
.
Function
A trimeric complex of the three proteins Mre11, RAD50RAD50 (gene)
DNA repair protein RAD50, also known as RAD50, is a protein that in humans is encoded by the RAD50 gene.- Function :The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and...
and NBS1 (XRS
XRS
Xerxes de Oliveira is a drum and bass producer from Brazil. He uses several pseudonyms including XRS, XRS Land, Friendtornik, and Kapitel 06...
in yeast), called the MRN
MRN
MRN may refer to:*Migrants Rights Network*Motor Racing Network*Mre11-Rad50-Nbs1 DNA damage repair complex*Magnetic Resonance Neurography*Medical Record Number*Mister Rogers' Neighborhood*Movement Reference Number, a term used in various customs...
complex in humans, recruits ATM to double strand breaks (DSBs) and holds the two ends together. ATM directly interacts with the NBS1 subunit and phosphorylates the histone variant H2AX on Ser139. This phosphorylation generates binding sites for adaptor proteins with a BRCT domain
BRCT domain
BRCA1 C Terminus domain is a family of evolutionarily related proteins.The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage, for example as found in the breast cancer DNA-repair protein BRCA1...
. These adaptor proteins then recruit different factors including the effector protein kinase CHK2 and the tumor suppressor p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
. The ATM-mediated DNA damage response consists of a rapid and a delayed response. The effector kinase CHK2 is phopsphorylated and thereby activated by ATM. Activated CHK2 phophorylates phosphatase CDC25A
CDC25A
Cell division cycle 25 homolog A , also known as CDC25A, is a mammalian gene.-Interactions:CDC25A has been shown to interact with ASK1, Epidermal growth factor receptor, C-Raf, CHEK1, Cyclin E1, PIM1 and YWHAB.-Further reading:...
which is degraded thereupon and can no longer dephosphororylate CDK2-Cyclin
Cyclin
Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase enzymes.- Function :...
resulting in cell-cycle arrest. If the DSB can not be repaired during this rapid response, ATM additionally phophorylates MDM2
Mdm2
Mdm2 is an important negative regulator of the p53 tumor suppressor. It is the name of a gene as well as the protein encoded by that gene. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain of the p53 tumor suppressor and an inhibitor of...
and p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
at Ser15. p53 is also phosphorylated by the effector kinase CHK2. These phosphorylation events lead to stabilization and activation of p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
and subsequent transcription of numerous p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
target genes including Cdk inhibitor p21
P21
p21 / WAF1 also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 is a protein that in humans is encoded by the CDKN1A gene located on chromosome 6 .- Function :...
which lead to long-term cell-cycle arrest or even apoptosis.
Regulation
A functional MRN complex is required for ATM activation after double strand breaks (DSBs). The complex functions upstream of ATM in mammalian cells and induces conformational changes that facilitate an increase in the affinity of ATM towards its substrates, such as CHK2 and p53P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
.
Inactive ATM is present in the cells without DSBs as dimers or multimers. Upon DNA damage, ATM autophosphorylates on residue Ser1981. This phosphorylation provokes dissociation of ATM dimers, which is followed by the release of active ATM monomers. Further autophosphorylation (of residues Ser367 and Ser1893) is required for normal activity of the ATM kinase. Activation of ATM by the MRN
MRN
MRN may refer to:*Migrants Rights Network*Motor Racing Network*Mre11-Rad50-Nbs1 DNA damage repair complex*Magnetic Resonance Neurography*Medical Record Number*Mister Rogers' Neighborhood*Movement Reference Number, a term used in various customs...
complex is preceded by at least two steps, i.e. recruitment of ATM to DSB ends by the mediator of DNA damage checkpoint protein 1 (MDC1
MDC1
Mediator of DNA damage checkpoint protein 1 is a protein that in humans is encoded by the MDC1 gene.-Interactions:MDC1 has been shown to interact with MRE11A, H2AFX and CHEK2.-Further reading:...
) which binds to MRE11, and the subsequent stimulation of kinase activity with the NBS1 C-terminus.
The three domains FAT, PRD and FATC are all involved in regulating the activity of the KD kinase domain. The FAT domain interacts with ATM's KD domain to stabilize the C-terminus region of ATM itself. The FATC domain is critical for kinase activity and highly sensitive to mutagenesis. It mediates protein-protein interaction for example with the histone acetyltransferase
Acetyltransferase
Acetyltransferase is a type of transferase enzyme that transfers an acetyl group.Examples include:* Histone acetyltransferases including CBP histone acetyltransferase* Choline acetyltransferase* Chloramphenicol acetyltransferase...
TIP60 (HIV-1 Tat interacting protein 60 kDa), which acetylates ATM on residue Lys3016. The acetylation occurs in the C-terminal half of the PRD domain and is required for ATM kinase activation and for its conversion into monomers. While deletion of the entire PRD domain abolishes the kinase activity of ATM, specific small deletions show no effect.
Role in cancer
Ataxia telangiectasiaAtaxia telangiectasia
Ataxia telangiectasia is a rare, neurodegenerative, inherited disease that affects many parts of the body and causes severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease...
(AT) is a rare human disease characterized by extreme cellular sensitivity to radiation and a predisposition to cancer. All AT patients contain mutations in the AT-mutated gene (ATM). Most other AT-like disorders are defective in genes encoding the MRN
MRN
MRN may refer to:*Migrants Rights Network*Motor Racing Network*Mre11-Rad50-Nbs1 DNA damage repair complex*Magnetic Resonance Neurography*Medical Record Number*Mister Rogers' Neighborhood*Movement Reference Number, a term used in various customs...
protein complex. One feature of the ATM protein is its rapid increase in kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
activity immediately following double-strand break formation. The phenotypic manifestation of AT is due to the broad range of substrates for the ATM kinase, involving DNA repair, apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, G1/S, intra-S checkpoint and G2/M checkpoints, gene regulation, translation
Translation
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. Whereas interpreting undoubtedly antedates writing, translation began only after the appearance of written literature; there exist partial translations of the Sumerian Epic of...
initiation
Initiation
Initiation is a rite of passage ceremony marking entrance or acceptance into a group or society. It could also be a formal admission to adulthood in a community or one of its formal components...
, and telomere
Telomere
A telomere is a region of repetitive DNA sequences at the end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Its name is derived from the Greek nouns telos "end" and merοs "part"...
maintenance. Therefore a defect in ATM has severe consequences in repairing certain types of damage to DNA, and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
may result from improper repair. AT patients have an increased risk for breast cancer that has been ascribed to ATM's interaction and phosphorylation of BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
and its associated proteins following DNA damage. Certain kinds of leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
s and lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s, including Mantle cell lymphoma
Mantle cell lymphoma
Mantle cell lymphoma is one of the rarest of the non-Hodgkin's lymphomas , comprising about 6% of NHL cases. There are only about 15,000 patients presently in the U.S. While it is difficult to treat and seldom considered cured, investigations into better treatments are actively pursued worldwide...
, T-ALL, atypical B cell chronic lymphocytic leukemia, and T-PLL are also associated with ATM defects.
Interactions
Ataxia telangiectasia mutated has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with RAD17
RAD17
Cell cycle checkpoint protein RAD17 is a protein that in humans is encoded by the RAD17 gene.-Interactions:RAD17 has been shown to interact with RAD9A, RAD1 homolog, POLE, NHP2L1, Ataxia telangiectasia mutated, HUS1 and Ataxia telangiectasia and Rad3 related.-Further reading:...
, RBBP8
RBBP8
Retinoblastoma-binding protein 8 is a protein that in humans is encoded by the RBBP8 gene.-Interactions:RBBP8 has been shown to interact with LMO4, Retinoblastoma-like protein 2, Retinoblastoma-like protein 1, Ataxia telangiectasia mutated, Retinoblastoma protein, CTBP1, SIAH1 and BRCA1.-Further...
, RAD51
RAD51
RAD51 is a human gene. The protein encoded by this gene is a member of the RAD51 protein family which assist in repair of DNA double strand breaks. RAD51 family members are homologous to the bacterial RecA and yeast Rad51...
, DNA-PKcs, RRM2B
RRM2B
Ribonucleoside-diphosphate reductase subunit M2 B is an enzyme that in humans is encoded by the RRM2B gene.-Interactions:RRM2B has been shown to interact with Mdm2 and Ataxia telangiectasia mutated.-Further reading:...
, FANCD2
FANCD2
Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation group currently includes FANCA, FANCB, FANCC, FANCD1 , FANCD2 , FANCE, FANCF, FANCG, and FANCL.- Function :Fanconi anemia is a genetically heterogeneous recessive disorder...
, Nibrin
Nibrin
Nibrin, also known as NBN, is a protein which in humans is encoded by the NBN gene.- Function :Nibrin is a protein associated with the repair of double strand breaks which pose serious damage to a genome. It is a 754 amino acid protein identified as a member of the NBS1/hMre11/RAD50 double strand...
, TERF1
TERF1
Telomeric repeat-binding factor 1 is a protein that in humans is encoded by the TERF1 gene.-Interactions:TERF1 has been shown to interact with SALL1, MAPRE1, NME1, TNKS2, Ataxia telangiectasia mutated, TINF2, TNKS, PINX1 and Abl gene....
, BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
, Abl gene
Abl gene
V-abl Abelson murine leukemia viral oncogene homolog 1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene located on chromosome 9.- Function :...
, TP53BP1
TP53BP1
Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the TP53BP1 gene.- Clinical significance :53BP1 is underexpressed in most cases of triple-negative breast cancer....
, MRE11A
MRE11A
Double-strand break repair protein MRE11A is a protein that in humans is encoded by the MRE11A gene.-Interactions:MRE11A has been shown to interact with Ku70, Ataxia telangiectasia mutated, MDC1, Rad50, Nibrin, TERF2 and BRCA1.-Further reading:...
, P53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, Bloom syndrome protein
Bloom syndrome protein
Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is expressed in Bloom syndrome.The Bloom syndrome gene product is related to the RecQ subset of DExH box-containing DNA helicases and has both DNA-stimulated ATPase and ATP-dependent DNA helicase activities...
, SMC1A
SMC1A
Structural maintenance of chromosomes protein 1A is a protein that in humans is encoded by the SMC1A gene.-Interactions:SMC1A has been shown to interact with SMC3 and Ataxia telangiectasia mutated.-External links:*...
and RHEB
RHEB
GTP-binding protein Rheb also known as Ras homolog enriched in brain is a protein that in humans is encoded by the RHEB gene.- Function :Rheb is a recently discovered member of the Ras superfamily that may be involved in neural plasticity...
.
Further reading
External links
- http://www.hprd.org/protein/06347
- Drosophila telomere fusion - The Interactive Fly
- GeneReviews/NCBI/NIH/UW entry on Ataxia telangiectasia
- OMIM entries on Ataxia telangiectasia