title: Chromatin regulates DNA torsional energy via topoisomerase II-mediated relaxation of positive supercoils.
abstract: Eukaryotic topoisomerases I (topo I) and II (topo II) relax the positive (+) and negative (-) DNA torsional stress (TS) generated ahead and behind the transcription machinery. It is unknown how this DNA relaxation activity is regulated and whether (+) and (-)TS are reduced at similar rates. Here, we used yeast circular minichromosomes to conduct the first comparative analysis of topo I and topo II activities in relaxing chromatin under (+) and (-)TS. We observed that, while topo I relaxed (+) and (-)TS with similar efficiency, topo II was more proficient and relaxed (+)TS more quickly than (-)TS. Accordingly, we found that the relaxation rate of (+)TS by endogenous topoisomerases largely surpassed that of (-)TS. We propose a model of how distinct conformations of chromatin under (+) and (-)TS may produce this unbalanced relaxation of DNA. We postulate that, while quick relaxation of (+)TS may facilitate the progression of RNA and DNA polymerases, slow relaxation of (-)TS may serve to favor DNA unwinding and other structural transitions at specific regions often required for genomic transactions.
authors.affiliation: Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fernández
authors.affiliation: Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.
authors.forename: Ofelia
authors.initials: O
authors.lastname: Díaz-Ingelmo
authors.affiliation: Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Martínez-García
authors.affiliation: Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain joaquim.roca@ibmb.csic.es.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Roca
mesh_terms: D002843:Chromatin; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D004278:DNA, Superhelical / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D002843:Chromatin; D004271:DNA, Fungal; D004278:DNA, Superhelical; D029701:Saccharomyces cerevisiae Proteins; D004250:DNA Topoisomerases, Type II
keywords: gyrase; nucleosome; supercoiling; transcription; yeast