Abstract
Mitotic chromosomes are long-known structures, but their internal organization and the exact process by which they are assembled are still a great mystery in biology. Topoisomerase II is crucial for various aspects of mitotic chromosome organization. The unique ability of this enzyme to untangle topologically intertwined DNA molecules (catenations) is of utmost importance for the resolution of sister chromatid intertwines. Although still controversial, topoisomerase II has also been proposed to directly contribute to chromosome compaction, possibly by promoting chromosome self-entanglements. These two functions raise a strong directionality issue towards topoisomerase II reactions that are able to disentangle sister DNA molecules (in trans) while compacting the same DNA molecule (in cis). Here, we review the current knowledge on topoisomerase II role specifically during mitosis, and the mechanisms that directly or indirectly regulate its activity to ensure faithful chromosome segregation. In particular, we discuss how the activity or directionality of this enzyme could be regulated by the SMC (structural maintenance of chromosomes) complexes, predominantly cohesin and condensin, throughout mitosis.
Highlights
Topoisomerase II is a homodimer that performs a unique role in living cells
Whereas some studies reveal it is virtually absent from mitotic chromosomes [112], others report an enrichment at pericentromeric regions, at the chromosomal axis, and at DNA bridges caused by topoisomerase II inhibition [113,114]
Cohesin may keep sister chromatids in such close proximity that biases topoisomerase reactions towards the intertwined state (Figure 3). In support of the latter is the finding that overexpression of topoisomerase II leads to sister chromatid re-entanglement, in a manner that depends on cohesin [19]. It has been extensively argued whether the presence of residual catenation in mitotic chromosomes is a by-product of DNA decatenation enzymology or, alternatively, this residual catenation may play a direct role in chromosome segregation
Summary
Topoisomerase II is a homodimer that performs a unique role in living cells. Besides the ability to change the supercoiling state of DNA that it shares with other types of topoisomerases, only topoisomerase II can untangle topologically intertwined DNA molecules (catenations). Analysis of the kinetics of sister chromatid resolution has been recently studied in great detail, either by using live cell imaging approaches, or methods that label individual sister chromatids [15,16] These studies revealed that the vast majority of mitotic entanglements between sister chromatids are resolved by the end of prophase, allowing clear individualization of two separate chromatid axes, a process dependent on topoisomerase II activity [15,16]. In contrast to this notion, recent findings provide a critical change in our understanding of chromosome resolution during mitosis by highlighting the reversibility of this process [18,19,20] (discussed in detail in Sections 5.4 and 5.5) These results highlight that previously separated DNA molecules are able to re-intertwine as a consequence of topoisomerase II action. PICH was recently shown to recruit and stimulate topoisomerase II activity to UFBs [32]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
