2026-06-14T03:30:18Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/189322025-05-07T10:12:16Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Jodkowska, Karolina
author
Pancaldi, Vera
author
Rigau, Maria
author
Almeida, Ricardo
author
Fernández-Justel, José M
author
Graña-Castro, Osvaldo
author
Rodríguez-Acebes, Sara
author
Rubio-Camarillo, Miriam
author
Carrillo-de-Santa-Pau, Enrique
author
Pisano, David
author
Al-Shahrour, Fatima
author
Valencia, Alfonso
author
Gómez, María
author
Méndez, Juan
funder
Ministerio de Ciencia y Tecnología (España)
funder
Fundação para a Ciência e Tecnologia (Portugal)
funder
Fundación La Caixa
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Foundation for Polish Science
2024-03-13T14:13:10Z
2024-03-13T14:13:10Z
2022-11-28
Nucleic Acids Res . 2022 ;50(21):12149-12165.
10.1093/nar/gkac1111
1362-4962
Nucleic acids research
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9757045/
36453993
http://hdl.handle.net/20.500.12105/18932
In mammalian cells, chromosomal replication starts at thousands of origins at which replisomes are assembled. Replicative stress triggers additional initiation events from 'dormant' origins whose genomic distribution and regulation are not well understood. In this study, we have analyzed origin activity in mouse embryonic stem cells in the absence or presence of mild replicative stress induced by aphidicolin, a DNA polymerase inhibitor, or by deregulation of origin licensing factor CDC6. In both cases, we observe that the majority of stress-responsive origins are also active in a small fraction of the cell population in a normal S phase, and stress increases their frequency of activation. In a search for the molecular determinants of origin efficiency, we compared the genetic and epigenetic features of origins displaying different levels of activation, and integrated their genomic positions in three-dimensional chromatin interaction networks derived from high-depth Hi-C and promoter-capture Hi-C data. We report that origin efficiency is directly proportional to the proximity to transcriptional start sites and to the number of contacts established between origin-containing chromatin fragments, supporting the organization of origins in higher-level DNA replication factories.
eng
3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.
journal article
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