Repair of apurinic/apyrimidinic sites in single-stranded DNA initiated by tyrosyl-DNA phosphodiesterase 1

Tyrosyl DNA phosphodiesterase 1 (Tdp1) is an enzyme that prevents the accumulation of covalent adducts of topoisomerase I (Top1) with DNA, it hydrolyzes 3' phosphotirosyl bonds. Human Tdp1 also possesses another activity: it is able to hydrolyze the apurinic/apyrimidinic (AP) site (both natural and its synthetic analogue, THF residue) located within the DNA strand. Mutation of Tdp1, which causes spinocerebellar ataxia with axonal neuropathy (SCAN1), leads to the loss of the AP cleaving activity of the enzyme