Three structural maintenance of chromosomes (SMC) complexes - cohesin, condensin and SMC5-SMC6 - are crucial for chromosome organization events in all domains of life. However, the roles of the Smc5/6 complex remain poorly understood, in spite of its association with human disease and cancers.
In a recent work, published in Nature Communications by researchers of IGM and IFOM, the authors identify that Smc5/6 roles in facilitating replication completion through difficult to replicate regions involves its tight functional interaction and cooperation with Sgs1-Top3-Rmi1, a helicase-topoisomerase protein complex conserved through evolution and mutated in the Bloom syndrome, the most cancer prone human disorder known to date. The authors reveal Smc5/6 as a critical orchestrator of this process of DNA replication, by bringing together several activities that can resolve or dissolve different DNA junctions, with the scope of linking the process of replication with local chromosome compaction required for chromosome segregation. Paradoxically at the first sight, these fundamental processes chromosome structure could be targetable in cancer cells, as tumor cells often suffer of aneuploidy and have even more chromosomes that need to be replicated, compacted and segregated.
Agashe S, Joseph CR, Reyes TAC, Menolfi D, Giannattasio M, Waizenegger A, Szakal B, Branzei D.
Smc5/6 functions with Sgs1-Top3-Rmi1 to complete chromosome replication at natural pause sites.
Nat Commun. 2021 Apr 8;12(1):2111. doi: 10.1038/s41467-021-22217-w.
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