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| Open AccessThe bacterial replication origin BUS promotes nucleobase capture
Here, the authors show that a DnaA:origin complex promotes specific nucleobase capture from a single DNA strand. It is proposed that this mechanism may play a key role stimulating opening of bacterial chromosome origins.
- Simone Pelliciari
- , Salomé Bodet-Lefèvre
- & Heath Murray
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Article
| Open AccessRIF1 regulates early replication timing in murine B cells
Here the authors show that in activated B cells, RIF1 primarily binds early-replicating active chromatin and promotes early replication. RIF1 and MCM proteins establish early replication timing signatures genome-wide and ensure early replication of highly transcribed genes.
- Daniel Malzl
- , Mihaela Peycheva
- & Rushad Pavri
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Article
| Open AccessORC1 binds to cis-transcribed RNAs for efficient activation of replication origins
Here the authors describe that the human origin recognition complex subunit 1 (ORC1) binds to RNAs transcribed from genes with origins of replication at their TSS impacting origin activation.
- Aina Maria Mas
- , Enrique Goñi
- & Maite Huarte
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Article
| Open AccessDNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation
RECQ4 mutations contribute to multiple developmental diseases and tumorigenesis. Here the authors describe how a highly oncogenic RECQ4 mutation alters the control of DNA synthesis, leading to abnormal DNA content and cell growth.
- Xiaohua Xu
- , Chou-Wei Chang
- & Yilun Liu
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Article
| Open AccessGlobal landscape of replicative DNA polymerase usage in the human genome
Profiling of human DNA polymerase Polε and Polα demonstrates their roles in leading and lagging strand DNA synthesis, and their independent measures allowed accurate predictions of replication dynamics and effects of transcription.
- Eri Koyanagi
- , Yoko Kakimoto
- & Yasukazu Daigaku
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Article
| Open AccessThe non-catalytic role of DNA polymerase epsilon in replication initiation in human cells
DNA polymerase epsilon has a critical role in DNA replication initiation. Here, the authors show that in human cancer cells POLE is dispensable for the replicative helicase assembly but not for replication initiation, which requires the non-catalytic domain of POLE1.
- Sameera Vipat
- , Dipika Gupta
- & Tatiana N. Moiseeva
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Article
| Open AccessStructural Insight into the MCM double hexamer activation by Dbf4-Cdc7 kinase
The Dbf4-dependent kinase Cdc7 (DDK) is essential for eukaryotic DNA replication. Here, the authors present a series of cryo-EM structures elucidating the versatility of this kinase in exerting an ordered phosphorylation of its essential target to promote replication initiation.
- Jiaxuan Cheng
- , Ningning Li
- & Yuanliang Zhai
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Article
| Open AccessStabilisation of half MCM ring by Cdt1 during DNA insertion
During pre-Replication Complex, eukaryotic cells load two MCMs into a head-to-head Double Hexamer around duplex DNA (DH). Here the authors preRC assembly assay with purified proteins to reveal insights into S. cerevisiae’s first steps that lead to the DH formation.
- Marina Guerrero-Puigdevall
- , Narcis Fernandez-Fuentes
- & Jordi Frigola
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| Open AccessA predictable conserved DNA base composition signature defines human core DNA replication origins
In metazoan the DNA sequence elements characterizing origin specification are unknown. By generating and analysing 19 SNS-seq datasets from different human cell types, the authors reveal a class and features of Core origins of replication which can be predicted by an algorithm.
- Ildem Akerman
- , Bahar Kasaai
- & Marcel Méchali
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| Open AccessThe ORC ubiquitin ligase OBI1 promotes DNA replication origin firing
DNA replication is initiated at defined genomic sites called origins of replication following ORC pre-replicative complex assembly. Here the authors identify a protein ubiquitylating ORC that is involved in origin activation and may act as a selector of origins to be fired.
- Philippe Coulombe
- , Joelle Nassar
- & Marcel Méchali
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| Open AccessStructure of DNA-CMG-Pol epsilon elucidates the roles of the non-catalytic polymerase modules in the eukaryotic replisome
Eukaryotic origin firing depends on assembly of the Cdc45-MCM-GINS (CMG) helicase, which requires the leading-strand polymerase Pol ɛ. Here the authors present a structural analysis of a CMG Pol ɛ on a DNA fork, providing insight on the steps leading productive helicase engagement to the DNA junction.
- Panchali Goswami
- , Ferdos Abid Ali
- & Alessandro Costa
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| Open AccessThe replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin
RepID has previously been shown to promote origin firing. Here the authors reveal that RepID regulates replication origins via the recruitment of the CRL4 complex, and prevents re-initiation and unscheduled DNA replication.
- Sang-Min Jang
- , Ya Zhang
- & Mirit I. Aladjem
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Article
| Open AccessEnsa controls S-phase length by modulating Treslin levels
The Greatwall/Ensa/PP2A-B55 pathway controls mitotic substrate phosphorylation and mitotic entry. Here the authors show that cells regulate S phase duration by controlling the ubiquitin-proteasome degradation of Treslin in a Gwl/Ensa-dependent pathway.
- Sophie Charrasse
- , Aicha Gharbi-Ayachi
- & Anna Castro
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Article
| Open AccessSUMO2/3 modification of cyclin E contributes to the control of replication origin firing
The organized initiation of DNA replication at sites throughout the genome must be carefully choreographed to maintain genome stability. Bonne-Andrea and colleagues show that protein SUMOylation controls the density of origin firing, and identify cyclin E as an important substrate in this context.
- Catherine Bonne-Andrea
- , Malik Kahli
- & Olivier Coux