Diphenyleneiodonium chloride, NO synthase

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

TDP1 (Tyrosyl-DNA phosphodiesterase 1) operates at a mechanical level to repair DNA by catalyzing the hydrolysis of phosphodiester bonds between tyrosyl residues and DNA. It is an important part of the DNA damage repair mechanism particularly in the repair of single-strand breaks. The protein weighs approximately 68 kDa and is ubiquitously expressed with significant levels found in the nucleus of cells. It's also known as SCAN1 and TRP1 reflecting its role in the repair of DNA strand breaks.

Biological function summary

TDP1 facilitates the repair of damaged DNA ensuring genomic stability. It plays an integral part of the DNA damage response complex interacting with other proteins like XRCC1 which assists in coordinating the repair of single-strand breaks. TDP1 acts by removing stalled topoisomerase 1-DNA covalent complexes thereby maintaining efficient DNA replication and transcription. The protein's activity is essential for proper cell cycle progression and cellular homeostasis.

Pathways

TDP1 is an important player in the DNA repair and base excision repair pathways. Its association with XRCC1 highlights its importance in the single-strand break repair pathway. Additionally TDP1 interacts with topoisomerase 1 to resolve topoisomerase-mediated DNA damage. These interactions are pivotal in ensuring proper repair mechanisms against genotoxic stress which maintains DNA integrity.

TDP1 is associated with neurodegenerative conditions and cancer. Mutations in TDP1 cause a rare disorder known as Spinocerebellar ataxia with axonal neuropathy (SCAN1) where DNA repair is compromised leading to neurodegeneration. TDP1's role in cancer comes from its ability to repair DNA damage from chemotherapeutic agents which sometimes leads to therapy resistance. Proteins like PARP play a significant role in these disorders as they are involved in poly(ADP-ribosyl)ation that assists TDP1 in DNA repair mechanisms.