DNA Damage Reversal

Direct reversal of DNA alkylation damage.

3.5.1. Alkylation Chemotherapy 10 3.5.2. Inhibition of hAGT by O6-Benzylguanine 10 3.5.3. Developing More Potent Inhibitors 10 3.6. Application of hAGT in Biotechnology 10 3.6.1. Quantification of AGT 10 3.6.2. Radioactive Imaging of Tumors 11 3.6.3. hAGT Fusion Proteins in Biotechnology 11 4. AlkB Proteins 11 4.1. Oxidative Dealkylation by AlkB 11 4.1.1. E. Coli AlkB 11 4.1.2. Puzzle of AlkB 1...

Reversal of DNA alkylation damage by two human dioxygenases.

The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the DNA lesions 1-methyladenine and 3-methylcytosine, which are generated in single-stranded stretches of DNA. AlkB is an alpha-ketoglutarate- and Fe(II)-dependent dioxygenase that oxidizes the relevant methyl groups and releases them as formaldehyde. Here, we identify two human AlkB homologs,...

Radiation track and DNA damage

Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity

DNA damage tolerance during eukaryotic replication is orchestrated by PCNA ubiquitination. While monoubiquitination activates mutagenic translesion synthesis, polyubiquitination activates an error-free pathway, elusive in mammals, enabling damage bypass by template switching. Fork reversal is driven in vitro by multiple enzymes, including the DNA translocase ZRANB3, shown to bind polyubiquitina...

Reversal of DNA damage induced Topoisomerase 2 DNA-protein crosslinks by Tdp2.

Mammalian Tyrosyl-DNA phosphodiesterase 2 (Tdp2) reverses Topoisomerase 2 (Top2) DNA-protein crosslinks triggered by Top2 engagement of DNA damage or poisoning by anticancer drugs. Tdp2 deficiencies are linked to neurological disease and cellular sensitivity to Top2 poisons. Herein, we report X-ray crystal structures of ligand-free Tdp2 and Tdp2-DNA complexes with alkylated and abasic DNA that ...