A Topology-Centric View on Mitotic Chromosome Architecture
Overview
Chemistry
Molecular Biology
Authors
Affiliations
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.
Compromised Mitotic Fidelity in Human Pluripotent Stem Cells.
Milagre I, Pereira C, Oliveira R Int J Mol Sci. 2023; 24(15).
PMID: 37569309 PMC: 10418648. DOI: 10.3390/ijms241511933.
A dual-function SNF2 protein drives chromatid resolution and nascent transcripts removal in mitosis.
Carmo C, Coelho J, Silva R, Tavares A, Boavida A, Gaetani P EMBO Rep. 2023; 24(9):e56463.
PMID: 37462213 PMC: 10481674. DOI: 10.15252/embr.202256463.
Separase and Roads to Disengage Sister Chromatids during Anaphase.
Konecna M, Abbasi Sani S, Anger M Int J Mol Sci. 2023; 24(5).
PMID: 36902034 PMC: 10003635. DOI: 10.3390/ijms24054604.
Morao A, Kim J, Obaji D, Sun S, Ercan S Mol Cell. 2022; 82(22):4202-4217.e5.
PMID: 36302374 PMC: 9837612. DOI: 10.1016/j.molcel.2022.10.002.
Topological gelation of reconnecting polymers.
Bonato A, Marenduzzo D, Michieletto D, Orlandini E Proc Natl Acad Sci U S A. 2022; 119(44):e2207728119.
PMID: 36279471 PMC: 9636914. DOI: 10.1073/pnas.2207728119.