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Role of Protein Linked DNA Breaks in Cancer

  • Walaa R. AllamEmail author
  • Mohamed E. Ashour
  • Amr A. Waly
  • Sherif El-KhamisyEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1007)

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.

Keywords

Protein linked DNA breaks Topoisomerases DAN repair Topoisomerases poisons Genome integrity 

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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  1. 1.Center for Genomics, Helmy Institute for Medical SciencesZewail City of Science and TechnologyGizaEgypt
  2. 2.Krebs Institute and Sheffield Institute for Nucleic Acids, Department of Molecular Biology and Biotechnology, Firth CourtUniversity of SheffieldSheffieldUK

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