Identification of formaldehyde-induced DNA-protein crosslinks by PxP-MS

Compromised enzymatic actions, reactive metabolites, and various chemotherapeutics cause toxic covalent DNA-protein crosslinks (DPCs). Failure to repair DPCs results in genomic instability, premature aging, and tumorigenesis. However, understanding the principles underlying DPC formation and repair has been hampered by a lack of methodologies to study DPCs in human cells. Here, we developed a technique for the Purification of x-linked Proteins (PxP), which allows identification and tracking of enzymatic and nonenzymatic DPCs. By combining PxP with quantitative proteomics, we investigated the nature of DPCs induced by formaldehyde.