Three prime repair exonuclease 1 is an enzyme that in humans is encoded by the TREX1 gene. [5] [6] [7] [8]
Three prime repair exonuclease 1 is an enzyme that in humans is encoded by the TREX1 gene. [5] [6] [7] [8]
This gene encodes the major 3'->5' DNA exonuclease in human cells. The protein is a non-processive exonuclease that may serve a proofreading function for a human DNA polymerase. It is also a component of the SET complex, and acts to rapidly degrade 3' ends of nicked DNA during granzyme A-mediated cell death. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, RVCL (Retinal Vasculopathy with Cerebral Leukodystrophy), and Cree encephalitis. Multiple transcript variants encoding different isoforms have been found for this gene. [8]
Mutations within the TREX1 gene cause familial chilblain lupus. The TREX1 polymorphisms confer susceptibility to systemic lupus erythematosus. Missense mutations of the TREX1 gene significantly downregulate its exonucleolytic capacity and result in the accumulation of nucleic acids. The build-up of the nucleic acids within the cytoplasm stimulates type-I interferon responses that could trigger autoimmune responses. [9] The region containing the TREX1 gene (3p21.31) has been linked to COVID-19 severity in a recent genome-wide association study. [10] This might explain the occurrence of chilblain like lesions in patients infected with SARS-CoV-2. [9]
TREX1 helps HIV‑1 to evade cytosolic sensing by degrading viral cDNA in the cytoplasm [11]
Mutations in TREX1 can give cause failure to appropriately remove ribonucleotides misincorporated into DNA. [12] The removal process is ordinary performed by ribonucleotide excision repair. In humans, a defect in this process can give rise to Aicardi-Goutieres syndrome involving microcephaly and neuroinflammation. [12]
TREX1 is the most abundant 3’-5’ DNA exonuclease in mammals. [13] Dominant C-terminal TREX1 genetic variants can disrupt homology-directed DNA repair and thus can trigger DNA damage and premature senescence phenotypes in humans, mice and Drosophila . [13] Such TREX1 variants can also cause adult onset small vessel disease known as vasculopathy with cerebral leukoencephalopathy. [13]
Ribonuclease H is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearly all organisms, from bacteria to archaea to eukaryotes.
Keratin 13 is a protein that in humans is encoded by the KRT13 gene.
Werner syndrome ATP-dependent helicase, also known as DNA helicase, RecQ-like type 3, is an enzyme that in humans is encoded by the WRN gene. WRN is a member of the RecQ Helicase family. Helicase enzymes generally unwind and separate double-stranded DNA. These activities are necessary before DNA can be copied in preparation for cell division. Helicase enzymes are also critical for making a blueprint of a gene for protein production, a process called transcription. Further evidence suggests that Werner protein plays a critical role in repairing DNA. Overall, this protein helps maintain the structure and integrity of a person's DNA.
Aprataxin is a protein that in humans is encoded by the APTX gene.
Three prime repair exonuclease 2 is an enzyme that in humans is encoded by the TREX2 gene.
DNA excision repair protein ERCC-8 is a protein that in humans is encoded by the ERCC8 gene.
McKusick–Kaufman/Bardet–Biedl syndromes putative chaperonin is a protein that in humans is encoded by the MKKS gene.
Colorectal mutant cancer protein is a protein that in humans is encoded by the MCC gene.
Cullin-7 is a RING-E3 ligase protein that in humans is encoded by the CUL7 gene.
Cytoplasmic dynein 2 heavy chain 1 is a protein that in humans is encoded by the DYNC2H1 gene.
T-box transcription factor TBX22 is a protein that in humans is encoded by the TBX22 gene.
DNA cross-link repair 1B protein is a protein that in humans is encoded by the DCLRE1B gene.
SAM domain and HD domain-containing protein 1 is a protein that in humans is encoded by the SAMHD1 gene. SAMHD1 is a cellular enzyme, responsible for blocking replication of HIV in dendritic cells, macrophages, monocytes and resting CD4+ T lymphocytes. It is an enzyme that exhibits phosphohydrolase activity, converting deoxynucleoside triphosphates (dNTPs) to inorganic phosphate (iPPP) and a 2'-deoxynucleoside (i.e. deoxynucleosides without a phosphate group). In doing so, SAMHD1 depletes the pool of dNTPs available to a reverse transcriptase for viral cDNA synthesis and thus prevents viral replication. SAMHD1 has also shown nuclease activity. Although a ribonuclease activity was described to be required for HIV-1 restriction, recent data confirmed that SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity.
Membrane frizzled-related protein is a protein that in humans is encoded by the MFRP gene.
Chilblain lupus erythematosus was initially described by Hutchinson in 1888 as an uncommon manifestation of chronic cutaneous lupus erythematosus. Chilblain lupus erythematosus is characterized by a rash that primarily affects acral surfaces that are frequently exposed to cold temperatures, such as the toes, fingers, ears, and nose. The rash is defined by oedematous skin, nodules, and tender plaques with a purple discoloration.
Hermansky–Pudlak syndrome 6 (HPS6), also known as ruby-eye protein homolog (Ru), is a protein that in humans is encoded by the HPS6 gene.
Ribonuclease H2 subunit A, also known as RNase H2 subunit A, is an enzyme that in humans is encoded by the RNASEH2A gene.
Ribonuclease H2, subunit B is a protein in humans that is encoded by the RNASEH2B gene. RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits, and it degrades the RNA of RNA:DNA hybrids. The non-catalytic B subunit of RNase H2 is thought to play a role in DNA replication.
Aicardi–Goutières syndrome (AGS), which is completely distinct from the similarly named Aicardi syndrome, is a rare, usually early onset childhood, inflammatory disorder most typically affecting the brain and the skin. The majority of affected individuals experience significant intellectual and physical problems, although this is not always the case. The clinical features of AGS can mimic those of in utero acquired infection, and some characteristics of the condition also overlap with the autoimmune disease systemic lupus erythematosus (SLE). Following an original description of eight cases in 1984, the condition was first referred to as 'Aicardi–Goutières syndrome' (AGS) in 1992, and the first international meeting on AGS was held in Pavia, Italy, in 2001.
Ribonuclease H2 subunit C is a protein that in humans is encoded by the RNASEH2C gene. RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits, and degrades the RNA of RNA:DNA hybrids.
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