Canonical non-homologous end-joining promotes genome mutagenesis and translocations induced by transcription-associated DNA topoisomerase 2 activity.

ABSTRACT: DNA topoisomerase II (TOP2) is a major DNA metabolic enzyme, with important roles in replication, transcription, chromosome segregation and spatial organisation of the genome. TOP2 is the target of a class of anticancer drugs that poison the DNA-TOP2 transient complex to generate TOP2-linked DNA double-strand breaks (DSBs). The accumulation of DSBs kills tumour cells but can also result in genome instability. The way in which topoisomerase activity contributes to transcription remains unclear. In this work we have investigated how transcription contributes to TOP2-dependent DSB formation, genome instability and cell death. Our results demonstrate that gene transcription is an important source of abortive TOP2 activity. However, transcription does not contribute significantly to apoptosis o

SUBMITTER: Olmedo-Pelayo J 

PROVIDER: S-EPMC7498328 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature