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TARDBP

TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa), is a protein that in humans is encoded by the TARDBP gene.

Function

TDP-43 is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. In particular, TDP-43 is a splicing factor binding to the intron8/exon9 junction of the CFTR gene and to the intron2/exon3 region of the apoA-II gene. A similar pseudogene is present on chromosome 20.

TDP-43 has been shown to bind both DNA and RNA and have multiple functions in transcriptional repression, pre-mRNA splicing and translational regulation. Recent work has characterized the transcriptome-wide binding sites revealing that thousands of RNAs are bound by TDP-43 in neurons.

TDP-43 was originally identified as a transcriptional repressor that binds to chromosomally integrated trans-activation response element (TAR) DNA and represses HIV-1 transcription. It was also reported to regulate alternate splicing of the CFTR gene and the apoA-II gene.

TDP1

Tyrosyl-DNA phosphodiesterase 1 is an enzyme that in humans is encoded by the TDP1 gene.

The protein encoded by this gene is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. Mutations in this gene are associated with the disease spinocerebellar ataxia with axonal neuropathy (SCAN1). While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same isoform.

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