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Condensin minimizes topoisomerase II-mediated entanglements of DNA in vivo

Since DNA molecules are extremely long, they have to be folded in close proximity inside the cell nucleus.

The juxtaposition of intracellular DNA segments, plus the DNA passage activity of topoisomerase II, then lead to the formation of DNA knots and interlinks that jeopardize genome transactions. Recent studies conducted by the DNA Topology Lab of the IBMB-CSIC uncovered that some mechanism minimizes the knotting probability of intracellular DNA. Now, DNA Topology Lab have tested whether this minimization is achieved via the intrinsic capacity of topoisomerase II to simplify the equilibrium topology of DNA; or whether it is mediated by SMC complexes, whose capacity to extrude DNA loops can enforce the dissolution of DNA knots by topoisomerase II. They discovered that the low knotting probability of DNA does not rely on the simplification capacity of topoisomerase II, nor on the activities of cohesin or the smc5/6 complex. However, inactivation of condensin boosts the occurrence of DNA knots throughout the cell cycle. These findings suggest a role for the DNA loop extrusion activity of condensin in vivo and may explain why condensin disruption produces many alterations in interphase chromatin in addition to the persistence of sister chromatid interlinks in mitotic chromatin.

 

Reference:

Condensin minimizes topoisomerase II-mediated entanglements of DNA in vivo

Sílvia Dyson, Joana Segura, Belén Martínez-García, Antonio Valdés, and Joaquim Roca*

The EMBO Journal  e105393 (2020)

DOI:  http://dx.doi.org/10.15252/embj.2020105393

DNA entanglements occur often within and across chromosomal regions. Condensin tightens these DNA entanglements and so enforces their dissolution by topoisomerase II. This process ensures accurate organization of chromatin during interphase, as well as proper segregation of chromosomes during cell division.

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