Origin licensing, also called pre-replicative complex (pre-RC) formation, occurs in late mitosis and during the G1 phase of the cell cycle. In human cells, DNA replication initiates from 20,000 to 50,000 replication origins selected from a five-В toВ tenfold excess of potential or вЂlicensedвЂ™ origins ( Moiseeva and Bakkenist, 2018 Papior et al., 2012). We discuss potential mechanisms specifying when and where replication initiates in human cells.

Interestingly, H4K20me3, a histone modification proposed to facilitate late origin licensing, was enriched in late-replicating initiation zones and gene deserts of stochastic replication fork direction. Therefore, ORC/MCM density correlates with replication timing but does not solely regulate the probability of replication initiation. Surprisingly, after controlling these variables, no difference in ORC/MCM density is detected between initiation zones, termination zones, unidirectionally replicating regions, and randomly replicating regions. Both, the origin recognition complex (ORC) and the minichromosome maintenance complex (MCM) are significantly and homogeneously depleted from transcribed genes, enriched at gene promoters, and more abundant in early- than in late-replicating domains. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with gene expression, replication timing, and fork directionality profiles obtained by RNA-seq, Repli-seq, and OK-seq. Claude Bernard, CNRS, Laboratoire de Physique, France Д®ukaryotic DNA replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Rheinische Friedrich-Wilhelms-UniversitГ¤t Bonn, Germany.German Center for Neurodegenerative Diseases (DZNE e.V.), Germany.Institute for Molecular Immunology, Monoclonal Antibody Core Facility, Helmholtz Zentrum MГјnchen, German Research Center for Environmental Health (GmbH), Germany.Laboratory for Functional Genome Analysis (LAFUGA), Gene Center of the Ludwig-Maximilians UniversitГ¤t (LMU) MГјnchen, Germany.Institut de Biologie de l'ENS (IBENS), DГ©partement de Biologie, Ecole Normale SupГ©rieure, CNRS, Inserm, PSL Research University, France.Research Unit Gene Vectors, Helmholtz Zentrum MГјnchen (GmbH), German Research Center for Environmental Health and German Center for Infection Research (DZIF), Germany.Research Unit Gene Vectors, Helmholtz Zentrum MГјnchen (GmbH), German Research Center for Environmental Health, Germany.

Solid project not showing up in mcm