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Lookup NU author(s): Professor Caroline AustinORCiD, Dr Ian CowellORCiD, Mushtaq Khazeem, Dawn Lok, Huei Teng Ng
This is the authors' accepted manuscript of a review published in its final definitive form in 2021. For re-use rights please refer to the publishers terms and conditions.
Transcription is regulated and mediated by multiprotein complexes in a chromatincontext. Transcription causes changes in DNA topology which is modulated by DNAtopoisomerases, enzymes that catalyse changes in DNA topology via transient breakingand re-joining of one or both strands of the phosphodiester backbone. Mammals havesix DNA topoisomerases, this review focuses on one, DNA topoisomerase II beta(TOP2B). In the absence of TOP2B transcription of many developmentally regulatedgenes is altered. Long genes seem particularly susceptible to the lack of TOP2B.Biochemical studies of the role of TOP2B in transcription regulated by ligands such asnuclear hormones, growth factors and insulin has revealed PARP1 associated withTOP2B and also PRKDC, XRCC5 and XRCC6. Analysis of publicly available databases ofprotein interactions confirms these interactions and illustrates interactions with other keytranscriptional regulators including TRIM28. TOP2B has been shown to interact with proteinsinvolved in chromosome organisation including CTCF and RAD21. Comparison ofpublicly available Chip-seq datasets reveals the location at which these proteins interactwith genes. The availability of resources such as large datasets of protein–protein interactions,e.g. BioGrid and IntAct and protein–DNA interactions such as Chip-seq in GEOenables scientists to extend models and propose new hypotheses.
Author(s): Austin CA, Cowell IG, Khazeem MM, Lok D, Ng HT
Publication type: Review
Publication status: Published
Journal: Biochemical Society Transactions
Year: 2021
Online publication date: 08/11/2021
Acceptance date: 11/10/2021
URL: https://doi.org/10.1042/BST20200454
DOI: 10.1042/BST20200454
PubMed id: PMID: 34747992
