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DNA replication timing (RT), reflecting the temporal order of origin activation, is known as a robust and conserved cell-type specific process. Upon low replication stress, the slowing of replication forks induces well-documented RT delays associated to genetic instability, but it can also generate RT advances that are still uncharacterized. In order to characterize these advanced initiation events, we monitored the whole genome RT from six independent human cell lines treated with low doses of aphidicolin. We report that RT advances are cell-type-specific and involve large heterochromatin domains. Importantly, we found that some major late to early RT advances can be inherited by the unstressed next-cellular generation, which is a unique process that correlates with enhanced chromatin accessibility, as well as modified replication origin landscape and gene expression in daughter cells. Collectively, this work highlights how low replication stress may impact cellular identity by RT advances events at a subset of chromosomal domains This work was supported by “la Ligue nationale contre le cancer” (LNCC labellisation to JSH and VB and the grants RS16/75-108 and RS17/75-135 to JCC), the “Institut National du Cancer” (INCA, PLBIO2016-10493 to JSH, VB and JCC), the “Centre de Recherches en Cancérologie de Toulouse” to VB, the “Laboratoire d’excellence Toulouse Cancer—TOUCAN” to JSH, the “Groupement des Entreprises Françaises contre le Cancer” (GEFLUC) to JCC, the “IdEx Université de Paris” (ANR-18-IDEX-0001) to JCC, the generous legacy from Ms Suzanne Larzat to JCC, and “la Fondation pour la Recherche Médicale” to LC. MM and VP were funded by INSERM, the “Fondation Toulouse Cancer Santé” and “Pierre Fabre Research Institute” as part of the Chair of Bioinformatics in Oncology of the CRCT.

The intrinsic dynamic nature of chromosomes is emerging as a fundamental component in regulating DNA transcription, replication, and damage-repair among other nuclear functions. With this increased awareness, reinforced over the last ten years, many new experimental techniques, mainly based on microscopy and chromosome conformation capture, have been introduced to study the genome in space and time. Owing to the increasing complexity of these cutting-edge techniques, computational approaches have become of paramount importance to interpret, contextualize, and complement such experiments with new insights. Hence, it is becoming crucial for experimental biologists to have a clear understanding of the diverse theoretical modeling approaches available and the biological information each of them can provide. M.A.M-R. acknowledges support from the European Union’s Seventh Framework Programme through the ERC (grant agreement 609989), European Union’s Horizon 2020 research and innovation programme (grant agreement 676556), and the Spanish Ministerio de Ciencia, Innovación y Universidades (BFU2017-85926-P). M.D.S. acknowledges support from the ORION project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement (grant agreement 741527). D.J. acknowledges Agence Nationale de la Recherche (ANR-18-CE12-0006-03, ANR-18-CE45-0022-01) for funding. CRG acknowledges support from ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208 and the CERCA Programme/Generalitat de Catalunya as well as support of the Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III and the EMBL partnership, the Generalitat de Catalunya through Departament de Salut and Departament d’Empresa i Coneixement, and the Co-financing with funds from the European Regional Development Fund (ERDF) by the Spanish Ministery of Science and Innovation coresponding to the Programa Opertaivo FEDER Plurirregional de España (POPE) 2014-2020 and by the Secretaria d'Universitats i Recerca, Departament d'Empresa i Coneixement of the Generalitat de Catalunya corresponding to the programa Operatiu FEDER Catalunya 2014-2020. Open Access fees paid from COST Action INC (CA18127), supported by COST (European Cooperation in Science and Technology)

Repetitive genome regions have been difficult to sequence, mainly because of the comparatively small size of the fragments used in assembly. Satellites or tandem repeats are very abundant in nematodes and offer an excellent playground to evaluate different assembly methods. Here, we compare the structure of satellites found in three different assemblies of the Caenorhabditis elegans genome: the original sequence obtained by Sanger sequencing, an assembly based on PacBio technology, and an assembly using Nanopore sequencing reads. In general, satellites were found in equivalent genomic regions, but the new long-read methods (PacBio and Nanopore) tended to result in longer assembled satellites. Important differences exist between the assemblies resulting from the two long-read technologies, such as the sizes of long satellites. Our results also suggest that the lengths of some annotated genes with internal repeats which were assembled using Sanger sequencing are likely to be incorrect.

1) The software package, including complete documentation and examples, is freely available to academic users from: http://www.ub.es/dnasp 2) Article espanyol més citat de la dècada 1999-2009, segons ScienceWatch (Set. 2010) DnaSP is a software package for the analysis of DNA polymorphism data. Present version introduces several new modules and features which, among other options allows, 1) handling big data sets (~5 Mbp per sequence); 2) conducting a large number of coalescent- based tests by Monte Carlo computer simulations; 3) extensive analyses of the genetic differentiation and gene flow among populations; 4) analysing the evolutionary pattern of preferred and unpreferred codons; 5) generating graphical outputs for an easy visualization of results. Peer Reviewed Award-winning