Cardamonin, anti-inflammatory spice-derived chalcone analog

Supplementary information

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TDP1 also known as tyrosyl-DNA phosphodiesterase 1 is an enzyme involved in DNA repair mechanisms. It has a pivotal role in resolving DNA single-strand breaks caused by topoisomerase I-DNA complexes. The enzyme weighs approximately 68 kDa. TDP1 is expressed in a variety of tissues including brain heart liver and kidneys. Its action is often associated with maintaining genomic integrity which is essential for cellular survival and function.

Biological function summary

TDP1 cooperates with other DNA repair proteins to facilitate the repair of damaged DNA. It forms part of the DNA repair complex working alongside proteins like XRCC1. This interaction highlights its importance in maintaining normal cellular processes. TDP1's enzymatic activity ensures the proper progression of DNA repair protecting cells from mutagenic threats and ensuring accurate replication.

Pathways

TDP1 functions within the base excision repair (BER) and non-homologous end joining (NHEJ) pathways which are important for mending DNA breaks. It interacts with proteins such as TOP1 to resolve DNA damage resulting from camptothecin treatment a chemotherapy drug. By coordinating with other molecules in these pathways TDP1 supports the integrity of the genome preventing aberrant genetic alterations.

TDP1 mutations are linked to certain neurodegenerative diseases like spinocerebellar ataxia with axonal neuropathy 1 (SCAN1). Besides contributing to neurodegenerative pathology alterations in TDP1 function are associated with cancer predisposition due to faulty DNA repair. In cancer proteins closely related to TDP1 such as PARP1 can be targeted therapeutically to enhance cancer cell susceptibility to treatment exploiting the DNA repair dependency of cancer cells.