DNA replication articles within Nature Communications

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  • Article
    | Open Access

    This study describes how p97Ufd1-Npl4 and the UBA-UBX protein Ubxn7 disassemble vertebrate replisomes during replication termination, and it provides novel insights into how p97 complexes assemble with UBA-UBX proteins on ubiquitylated substrates

    • Olga V. Kochenova
    • , Sirisha Mukkavalli
    •  & Johannes C. Walter

  • Article
    | Open Access

    DNA replication stress can result in genome instability. Here the authors show that the ubiquitin like modifier protein, ISG15, important during the innate immune response, acts at replication forks to mitigate DNA replication stress.

    • Christopher P. Wardlaw
    •  & John H. J. Petrini

  • Article
    | Open Access

    Most eukaryotes do not use a consensus DNA sequence as binding sites for the origin recognition complex (ORC) to initiate DNA replication, however budding yeast do. Here the authors show S. cerevisiae ORC can bind nucleosomes near nucleosome-free regions and recruit replicative helicases to form a pre-replication complex independent of the DNA sequence.

    • Sai Li
    • , Michael R. Wasserman
    •  & Shixin Liu

  • Article
    | Open Access

    DNA replication of repetitive sequences was recreated in a test tube using purified components. DNA alone was sufficient to induce stalling. Both stalling and recovery were dictated by the capacity of DNA to fold into unusual secondary structures.

    • Corella S. Casas-Delucchi
    • , Manuel Daza-Martin
    •  & Gideon Coster

  • Article
    | Open Access

    The range of available copy numbers for cloning vectors is largely restricted to the handful of ORIs that have been isolated from plasmids found in nature. Here the authors introduce a plasmid system that allow for the continuous, finely-tuned control of plasmid copy number between 1 and 800 copies per cell.

    • Miles V. Rouches
    • , Yasu Xu
    •  & Guillaume Lambert

  • Article
    | Open Access

    How nucleosome assembly of parental histones is regulated following DNA replication is still an open question. Here the authors show that unlike deposition of new histones H3.1 and H3.3 that utilizes different histone chaperones, parental H3.1 and H3.3 are both stably inherited during mitotic cell division in mouse embryonic stem cells, and this involves histone chaperones Mcm2, Pole3 and Pole4.

    • Xiaowei Xu
    • , Shoufu Duan
    •  & Zhiguo Zhang

  • Article
    | Open Access

    A scalable approach to explore DNA replication in single cells reveals that although aneuploidy does not have a major impact on the pattern of replication, different cell types and sub-populations display distinguished replication paths.

    • Stefano Gnan
    • , Joseph M. Josephides
    •  & Chun-Long Chen

  • Article
    | Open Access

    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

  • Article
    | Open Access

    DNA primases initiate a short primer before handing off to DNA polymerases to continue replication. Here the authors reveal a unique ability of archaeal primases to first synthesize RNA before stochastically incorporating a deoxyribonucleotide and further extending the primer as DNA.

    • Mark D. Greci
    • , Joseph D. Dooher
    •  & Stephen D. Bell

  • Article
    | Open Access

    Loss of BRCA1 or BRCA2 results in genomic instability; however most studies have focused on the role of these proteins in double-strand break repair. Here the authors coupled cell line genetics and whole genome sequencing to investigate the formation of base substitutions and short indels in BRCA1-deficient cells, revealing a role for translesion DNA synthesis regulated by 53BP1.

    • Dan Chen
    • , Judit Z. Gervai
    •  & Dávid Szüts

  • Article
    | Open Access

    The tumor suppressor BRCA2 protects stalled DNA replication forks from unrestrained degradation; however the mechanism whereby unprotected stalled forks are preserved and restarted has remained elusive. Here the authors show that the WRN helicase promotes stalled fork recovery and limits fork hyper-degradation in the absence of BRCA2 protection.

    • Arindam Datta
    • , Kajal Biswas
    •  & Robert M. Brosh Jr

  • Article
    | Open Access

    Tumor suppressor BRCA2 is known to stabilize and restart stalled DNA replication forks. Here the authors show that BRCA2 is recruited to the replication fork through its interaction with MCM10 and inhibits Primase-Polymerase-mediated repriming, lesion bypass and single strand DNA gap formation after DNA damage.

    • Zhihua Kang
    • , Pan Fu
    •  & Bing Xia

  • Article
    | Open Access

    Replicative hexameric helicases are fundamental components of replisomes. Here the authors resolve a cryo-EM structure of the E1 helicase from papillomavirus bound to a DNA replication fork, providing insights into the mechanism of DNA unwinding by these hexameric enzymes.

    • Abid Javed
    • , Balazs Major
    •  & Elena V. Orlova

  • Article
    | Open Access

    RAD51 is a well known player of DNA repair and homologous recombination. Here the authors reveal a function for RAD51 in protecting under-replicated DNA in mitotic human cells, promoting mitotic DNA synthesis (MiDAS) and successful chromosome segregation.

    • Isabel E. Wassing
    • , Emily Graham
    •  & Fumiko Esashi

  • Article
    | Open Access

    The BRCA1-PALB2-BRCA2-RAD51 (BRCA1-P) complex is well known to play a fundamental role in DNA repair, but how the complex recruitment is regulated is still a matter of interest. Here the authors reveal mechanistic insights into RNF168 activity being responsible for PALB2 recruitment, through BARD1-BRCA1 during homologous recombination repair.

    • John J. Krais
    • , Yifan Wang
    •  & Neil Johnson

  • Article
    | Open Access

    Germline mutations in BRCA1 or BRCA2 tumour suppressor genes predispose to different cancers, as does oncogene activation. Here the authors reveal that aberrant transcription of specific genes triggered by activation of the oncogene β-catenin causes replication failure and cell death in the context of BRCA1/2 deficiency.

    • Rebecca A. Dagg
    • , Gijs Zonderland
    •  & Madalena Tarsounas

  • Perspective
    | Open Access

    A key feature of living cells is the cell cycle. In this Perspective, the authors explore attempts to recreate this process and what is still required for an integrated synthetic cell cycle.

    • Lorenzo Olivi
    • , Mareike Berger
    •  & John van der Oost

  • Article
    | Open Access

    Tpr nucleoporin is known to be essential for nuclear transport and mitosis processes. Here the authors explore the link between Tpr and genome instability providing insights into the role of Tpr in safeguarding cells from RNA-mediated replication stress.

    • Martin Kosar
    • , Michele Giannattasio
    •  & Marco Foiani

  • Article
    | Open Access

    Single-stranded DNA during DNA replication and repair in S/G2 needs protection by replication protein A (RPA). Here the authors reveal that RPA also shields inherited single-stranded DNA in G1, representing replication remnants from the previous cell cycle, to allow for post-mitotic DNA synthesis.

    • Aleksandra Lezaja
    • , Andreas Panagopoulos
    •  & Matthias Altmeyer

  • Article
    | Open Access

    BRCA1-mediated resolution of R-loops has previously been described. Here the authors reveal a functional association of BRCA1 with TERRA RNA at telomeres, which develops in an R-loop-, and a cell cycle-dependent manner.

    • Jekaterina Vohhodina
    • , Liana J. Goehring
    •  & David M. Livingston

  • Article
    | Open Access

    DNA replication processes are often dysregulated in cancer. Here the authors analyse DNA synthesis patterns in cancer cells undergoing partial genome re-replication to reveal that re-replication exhibits aberrant replication fork dynamics and a skewed distribution of replication initiation that over-duplicates early-replicating genomic regions.

    • Haiqing Fu
    • , Christophe E. Redon
    •  & Mirit I. Aladjem

  • Article
    | Open Access

    Different proteins localised at telomeres ensure chromosome end stability to prevent double strand-end break recognition. Here the authors provide new insight into how in S. cerevisiae the interaction between Rif2 and Rad50 inhibits MRX functions at telomeres.

    • Florian Roisné-Hamelin
    • , Sabrina Pobiega
    •  & Stéphane Marcand

  • Article
    | Open Access

    In the genome, repetitive guanine-rich sequences have the potential to spontaneously fold into non-canonical DNA secondary structures known as G-quadruplex (G4). Using novel single-molecule imaging approaches, the authors reveal that G4 formation within active replication forks locally perturb replisome dynamics and damage response signaling, which require RPA and FANCJ for regulation.

    • Wei Ting C. Lee
    • , Yandong Yin
    •  & Eli Rothenberg

  • Article
    | Open Access

    Eukaryotic DNA replication is regulated to ensure copying of the genome (only) once per cell cycle. Here the authors, using optical trapping and confocal microscopy, demonstrate the dynamics of the origin recognition complex and subsequent intermediates that lead up to the loading of an MCM helicase onto DNA.

    • Humberto Sánchez
    • , Kaley McCluskey
    •  & Nynke H. Dekker

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Most regions of the mammalian genome replicate both alleles in a synchronous manner, but some loci have been found to replicate asynchronously and the time of replication of each allele is different. Here the authors, by employing clonal mouse cells from a hybrid strain chart replication timing over the entire genome, using polymorphisms to distinguish between the paternal and maternal alleles.

    • Britny Blumenfeld
    • , Hagit Masika
    •  & Itamar Simon

  • Article
    | Open Access

    Replication forks that are stalled at obstacles on the DNA template can be restarted by homologous recombination. Here, the authors show replication dynamics during homologous recombination-dependent replication fork restart by combining polymerase usage sequencing and a Monte Carlo mathematical model.

    • Karel Naiman
    • , Eduard Campillo-Funollet
    •  & Antony M. Carr

  • Article
    | Open Access

    The BLM helicase interacts with the topoisomerase TOP3A and RMI1 to form the BTR complex. Here, the authors reveal that this complex contains multiple binding sites for the single-stranded DNA-binding complex RPA, and that RPA-binding stimulates BLM recruitment to stalled replication forks to promote their restart after replication stress.

    • Ann-Marie K. Shorrocks
    • , Samuel E. Jones
    •  & Andrew N. Blackford

  • Article
    | Open Access

    Rad5 is a hub connecting three replication stress tolerance pathways. Here, the authors present the 3.3 Å crystal structure of a N-terminal truncated K.lactis Rad5 construct that reveals the spatial arrangement of the HIRAN, Snf2 and RING domains and structure-guided in vitro and in vivo experiments reveal multiple activities of the yeast Rad5 HIRAN domain among them a role in binding PCNA and supporting its ubiquitination.

    • Miaomiao Shen
    • , Nalini Dhingra
    •  & Song Xiang

  • Article
    | Open Access

    The role of cohesin in organizing a functional nuclear architecture remains poorly understood. Here the authors show that cohesin depleted cells pass through endomitosis forming a multilobulated nucleus able to proceed through S-phase with typical features of active and inactive nuclear compartments and spatio-temporal patterns of replication domains.

    • Marion Cremer
    • , Katharina Brandstetter
    •  & Thomas Cremer

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