2026/06/07 by Korak Kumar Ray, Artur Kaczmarczyk, Alasdair D. J. Freeman +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · Engineering · #Advanced biosensing and bioanalysis techniques #Anatomy #Biology #Biophysics #Bridge (graph theory) #Chemistry #Composite material #Computer science #DNA #DNA and Nucleic Acid Chemistry #Endonuclease #Engineering #Genetics #Materials science #Process (computing) #RNA Interference and Gene Delivery #Structural engineering #Tension (geology)
paper · doi:10.1093/nar/gkag585
published in Nucleic Acids Research 54(11) (Oxford University Press)
openalex created_date 2025/10/10 · openalex publication_date 2026/06/07 · openalex updated_date 2026/08/01
Covalent linkages between chromosomes form naturally as a result of recombination or DNA replication. These can persist until late mitosis, resulting in the formation of ultrafine bridges, preventing cell division and causing genome instability through mechanical DNA rupture. The endonuclease ANKLE1, selective for DNA branchpoints during cytokinesis and localizing at the cell midbody, is ideally poised to act as the 'enzyme of last resort' in processing interchromosomal bridges, thereby allowing cell division. How ANKLE1 catalyzes DNA cleavage under the high tension that exists in interchromosomal bridges during mitosis remains unexplored. Using optical tweezers, we show that ANKLE1 is a mechanosensitive endonuclease whose catalytic activity is stimulated by tension in its DNA substrate. At high tension, we observe that the rate at which ANKLE1 catalyzes the cleavage of DNA junctions increases continuously with applied tension, with a 20-fold increase in the cleavage rate at 60 pN. This indicates that ANKLE1 has evolved to detect and respond to tension-induced changes to the DNA structure in a manner that facilitates nucleolytic activity. This mechanoenzymological response of ANKLE1 to tension within its DNA substrate reveals how this enzyme is well suited to its suggested biological role as an ultrafine-bridge processing enzyme during late mitosis.