Specialized topoisomerases solve the topological constraints arising when replication forks encounter transcription. We have investigated the contribution of Top2 in S phase transcription. Specifically in S phase, Top2 binds intergenic regions close to transcribed genes. The Top2-bound loci exhibit low nucleosome density and accumulate gammaH2A when Top2 is defective. These intergenic loci associate with the HMG protein Hmo1 throughout the cell cycle and are refractory to the histone variant Htz1. In top2 mutants, Hmo1 is deleterious and accumulates at pericentromeric regions in G2/M. Our data indicate that Top2 is dispensable for transcription and that Hmo1 and Top2 bind in the proximity of genes transcribed in S phase suppressing chromosome fragility at the M-G1 transition. We propose that an Hmo1-dependent epigenetic signature together with Top2 mediate an S phase architectural pathway to preserve genome integrity.

Genome-organizing factors Top2 and Hmo1 prevent chromosome fragility at sites of S phase transcription / R. Bermejo, T. Capra, V. Gonzalez-Huici, D. Fachinetti, A. Cocito, G. Natoli, Y. Katou, H. Mori, K. Kurokawa, K. Shirahige, M. Foiani. - In: CELL. - ISSN 0092-8674. - 138:5(2009 Sep 04), pp. 870-884.

Genome-organizing factors Top2 and Hmo1 prevent chromosome fragility at sites of S phase transcription

T. Capra
Secondo
;
D. Fachinetti;H. Mori;M. Foiani
Ultimo
2009-09-04

Abstract

Specialized topoisomerases solve the topological constraints arising when replication forks encounter transcription. We have investigated the contribution of Top2 in S phase transcription. Specifically in S phase, Top2 binds intergenic regions close to transcribed genes. The Top2-bound loci exhibit low nucleosome density and accumulate gammaH2A when Top2 is defective. These intergenic loci associate with the HMG protein Hmo1 throughout the cell cycle and are refractory to the histone variant Htz1. In top2 mutants, Hmo1 is deleterious and accumulates at pericentromeric regions in G2/M. Our data indicate that Top2 is dispensable for transcription and that Hmo1 and Top2 bind in the proximity of genes transcribed in S phase suppressing chromosome fragility at the M-G1 transition. We propose that an Hmo1-dependent epigenetic signature together with Top2 mediate an S phase architectural pathway to preserve genome integrity.
DNA topoisomerase-II; ribosomal-protein genes; saccharomyces-cerevisiae; replication fork; binding proteins; checkpoint pathways; damage response; helicase RRM3P; box protein; cell-cycle
Settore BIO/11 - Biologia Molecolare
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/658434
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