During DNA replication, DNA helicases separate the complementary DNA strands; this process of unwinding produces torsional stress in the DNA, which is relieved by topoisomerases. It would not be surprising, therefore, if DNA helicases were to operate in close conjuction with topoisomerases. This has been shown for certain RecQ helicases.

For example, E.coli RecQ helicase can unwind a covalently-closed double-stranded DNA substrate, and this activity stimulates E.coli topoisomerase III to fully catenate (interlink) two or more plasmid molecules.

BLM also interacts with topoisomerase III, via both the N- and C-terminal domains of BLM. To date, only an interaction with one of the two human topoisomerase III isoforms, TOPO III , has been shown. The finding of two binding sites on BLM for TOPO III suggests that these proteins might interact in a 1:2 ratio.

Since topoisomerase III enzymes only make single-stranded DNA nicks, the incorporation of two topoisomerase molecules could allow double-strand breaks to take place. This could help to disrupt recombination intermediates between inappropriately paired DNA strands.

Pathology

 germline mutations of TOP3 in the Smith-Magenis syndrome (MIM.182290)

See also

 topoisomerases (TOPs)