期刊
DNA REPAIR
卷 94, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.dnarep.2020.102900
关键词
Topoisomerases; PARP; DNA damage; SSB; DSB; DNA strand break; TDP1; TDP2; TOP1; TOP2
资金
- MRC [MR/P010121/1]
- CRUK [C6563/A7322]
- ERC Advanced Investigator Award [SIDSCA694996]
- Royal Society Wolfson Research Merit Award
- CRUK Program grant [C6/A18796]
DNA topoisomerases alleviate the torsional stress that is generated by processes that are central to genome metabolism such as transcription and DNA replication. To do so, these enzymes generate an enzyme intermediate known as the cleavage complex in which the topoisomerase is covalently linked to the termini of a DNA single- or double-strand break. Whilst cleavage complexes are normally transient they can occasionally become abortive, creating protein-linked DNA breaks that threaten genome stability and cell survival; a process promoted and exploited in the cancer clinic by the use of topoisomerase 'poisons'. Here, we review the consequences to genome stability and human health of abortive topoisomerase-induced DNA breakage and the cellular pathways that cells have adopted to mitigate them, with particular focus on an important class of enzymes known as tyrosyl-DNA phosphodiesterases.
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