Rotation of DNA around intact strand in human topoisomerase I implies distinct mechanisms for positive and negative supercoil relaxation.

ABSTRACT: Topoisomerases are enzymes of quintessence to the upkeep of superhelical DNA, and are vital for replication, transcription and recombination. An atomic-resolution model for human topoisomerase I in covalent complex with DNA is simulated using molecular dynamics with external potentials that mimic torque and bias the DNA duplex downstream of a single-strand cut to rotate around the intact strand, according to the prevailing enzymatic mechanism. The simulations reveal the first dynamical picture of how topoisomerase accommodates large-scale motion of DNA as it changes its supercoiling state, and indicate that relaxation of positive and negative supercoils are fundamentally different. To relax positive supercoils, two separate domains (the 'lips') of the protein open up by about 10-14 A, wher

SUBMITTER: Sari L 

PROVIDER: S-EPMC1298917 | biostudies-literature | 2005

REPOSITORIES: biostudies-literature