The Induction and Repair of DNA-Protein Crosslinks in Mammalian Cells (pp. 347-378)
Authors: (Sharon Barker, Michael Weinfeld and David Murray, Department of Oncology, Division of Experimental Oncology, University of Alberta, Edmonton, Alberta, Canada)
Abstract: DNA-protein crosslinks (DPCs), which are generated by covalent linkage of proteins
to the DNA duplex, comprise an under-studied class of DNA lesions. They can be
induced by commonly encountered agents including environmental chemicals, cancerchemotherapeutic
drugs and ionizing radiation. DPCs could pose a serious threat to
cellular function because they may disrupt the progression of the replication and
transcription machineries. A number of problems have plagued researchers examining
this type of DNA damage. Many agents can induce DPCs by more than one chemical
mechanism. Furthermore, these agents invariably induce other types of DNA damage.
Measurements of DPC damage have also been hampered by the lack of stringent and
sensitive methodologies for their isolation. However, recent advances in DPC-isolation
methodology have allowed for more in-depth analyses of these lesions. Additionally,
advances in the study of chromatin structure have provided further understanding of the
influence of chromatin dynamics on the induction and repair of DPCs. At the same time,
our improving knowledge of many DNA-repair pathways has afforded opportunities for
assessing the involvement of these pathways in the removal of DPCs from the genome.
This chapter will discuss the impact of these advances on our understanding of DPCs and
their biological consequences.