Ubiquitin and Ubiquitin-Like Proteins in Repair of Topoisomerase-Mediated DNA Damage

  • Shyamal D. Desai
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Topoisomerases are enzymes involved in various cellular DNA transactions (Chen and Liu 1994; Li and Liu 2001; Pommier 1996; Wang 2002) (see Chaps. 1–5). The main function of all topoisomerases is to dissipate the torsional stress (supercoiling of the DNA) generated during DNA transactions such as transcription, replication, chromosome condensation, and segregation (Castano et al. 1996; Champoux 2001; Leppard and Champoux 2005; Zhang et al. 1988, 2000). To date, four type I DNA topoisomerases have been identified and characterized in human cells: nuclear Top1 (Top1) (Liu 1983; Wang 2002), mitochondrial topoisomerase (Top1mt) (Zhang et al. 2001), Top3α (Li and Wang 1998), and Top3β (Wilson et al. 2000) (see Chap. 1). Two type II human topoisomerases have been identified: Top2α and Top2β (Nitiss 2009a). Human topoisomerase I (Top1) is a type IB topoisomerase (forms 3′-phosphotyrosyl linkage with DNA) that functions as a swivel in DNA replication, RNA transcription, and chromosome condensation and segregation (Champoux 2001; Liu 1983). Human Top3α (Top3α) is a type IA (forms 5′-DNA tyrosyl linkages) topoisomerase and is essential for early embryogenesis, as evidenced by mouse knockout studies (Li and Wang 1998). Human Top3β is also a type 1A topoisomerase; although the Top3β knockout mouse develops to maturity, its mean lifespan is reduced (Kwan and Wang 2001). Thus, it appears that Top3α and β do not complement each other despite of their very similar enzymatic characteristics.


Cleavable Complex SUMOylation Site E3ub Ligase Synergistic Anticancer Activity Top2 Poison 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyLSU Health Sciences Center-School of MedicineNew OrleansUSA

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