TDP2

Description

The TDP2 (tyrosyl-DNA phosphodiesterase 2) is a protein-coding gene located on chromosome 6.

TDP2 is a DNA repair enzyme that removes various covalent adducts from DNA by hydrolyzing a 5'-phosphodiester bond, producing DNA with a free 5' phosphate. It catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. This 5'-tyrosyl DNA phosphodiesterase activity allows the repair of TOP2-induced DNA double-strand breaks (DSBs) without requiring nuclease activity, generating 'clean' DSBs with 5'-phosphate termini ready for ligation. This protects the transcription of genes involved in neurological development and maintenance from TOP2's abortive activity. TDP2 hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DSBs caused by radiation and free radicals. It prefers single-stranded DNA or duplex DNA with a 4 base pair overhang as a substrate. TDP2 acts as a regulator of ribosome biogenesis following stress. It also has 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and slower than TDP1. TDP2 is the major, if not the only, 5'-tyrosyl-DNA phosphodiesterase in cells. TDP2 functions as an adapter in the specific activation of MAP3K7/TAK1 in response to TGF-beta. It associates with components of the TGF-beta receptor-TRAF6-TAK1 signaling module and promotes their ubiquitination-dependent complex formation. TDP2 is involved in non-canonical TGF-beta-induced signaling pathways. It may also negatively regulate ETS1 and inhibit NF-kappa-B activation.

TDP2 is also known as AD022, EAP2, EAPII, TTRAP, dJ30M3.3, hTDP2.

Associated Diseases

• Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to TUD deficiency
• Spinocerebellar ataxia, autosomal recessive 23