Role of Protein Linked DNA Breaks in Cancer

Abstract

Topoisomerases are a group of specialized enzymes that function to maintain DNA topology by introducing transient DNA breaks during transcription and replication. As a result of abortive topoisomerases activity, topoisomerases catalytic intermediates may be trapped on the DNA forming topoisomerase cleavage complexes (Topcc). Topoisomerases trapping on the DNA is the mode of action of several anticancer drugs, it lead to formation of protein linked DAN breaks (PDBs). PDBs are now considered as one of the most dangerous forms of endogenous DNA damage and a major threat to genomic stability. The repair of PDBs involves both the sensing and repair pathways. Unsuccessful repair of PDBs leads to different signs of genomic instabilities such as chromosomal rearrangements and cancer predisposition. In this chapter we will summarize the role of topoisomerases induced PDBs, identification and signaling, repair, role in transcription. We will also discuss the role of PDBs in cancer with a special focus on prostate cancer.

Increased genomic instability following treatment with direct acting anti-hepatitis C virus drugs

“…In this regard, our findings of reduced baseline topoisomerases 1 and 2 (TOPs) expression in MCV patients are consistent with other studies of decreased TOP1 activity in patients with autoimmune diseases [ 60 ]. Unfaithful TOPs activity is involved in developing several human diseases [ [61] , [62] , [63] ]. Furthermore, TOP1 inhibition was suggested to suppress microbial activated genes [ 64 ] and thus our data suggest a role for TOPs in driving host inflammation in the context of HCV-MCV.…”