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Genes 2016, 7(7), 32; doi:10.3390/genes7070032

Collision of Trapped Topoisomerase 2 with Transcription and Replication: Generation and Repair of DNA Double-Strand Breaks with 5′ Adducts

Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
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Author to whom correspondence should be addressed.
Academic Editor: Richard T. Pomerantz
Received: 6 May 2016 / Revised: 17 June 2016 / Accepted: 24 June 2016 / Published: 1 July 2016
(This article belongs to the Special Issue Replication and Transcription Associated DNA Repair)
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Abstract

Topoisomerase 2 (Top2) is an essential enzyme responsible for manipulating DNA topology during replication, transcription, chromosome organization and chromosome segregation. It acts by nicking both strands of DNA and then passes another DNA molecule through the break. The 5′ end of each nick is covalently linked to the tyrosine in the active center of each of the two subunits of Top2 (Top2cc). In this configuration, the two sides of the nicked DNA are held together by the strong protein-protein interactions between the two subunits of Top2, allowing the nicks to be faithfully resealed in situ. Top2ccs are normally transient, but can be trapped by cancer drugs, such as etoposide, and subsequently processed into DSBs in cells. If not properly repaired, these DSBs would lead to genome instability and cell death. Here, I review the current understanding of the mechanisms by which DSBs are induced by etoposide, the unique features of such DSBs and how they are repaired. Implications for the improvement of cancer therapy will be discussed. View Full-Text
Keywords: topoisomerase 2; DNA double-strand breaks (DSBs); DSB repair; 5′ strand resection; 5′ adducts; Mre11; CtIP; DNA2 topoisomerase 2; DNA double-strand breaks (DSBs); DSB repair; 5′ strand resection; 5′ adducts; Mre11; CtIP; DNA2
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Yan, H.; Tammaro, M.; Liao, S. Collision of Trapped Topoisomerase 2 with Transcription and Replication: Generation and Repair of DNA Double-Strand Breaks with 5′ Adducts. Genes 2016, 7, 32.

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