DNA replication articles within Nature

  • Article
    | Open Access

    The Polα–primase-associated CST complex organizes telomeric C-strand DNA synthesis, and, in combination with telomerase, it carries out complete replication of the single-stranded DNA overhang found at human telomeres.

    • Arthur J. Zaug
    • , Karen J. Goodrich
    •  & Thomas R. Cech
  • Article
    | Open Access

    Cryo-electron microscopy structures of the sequential assembly of the CMG replicative helicase on a chromatinized origin of replication provide insights into the mechanism through which DNA melting is initiated by ATP binding.

    • Jacob S. Lewis
    • , Marta H. Gross
    •  & Alessandro Costa
  • Article
    | Open Access

    A study shows that the three-dimensional conformation of the human genome influences the positioning of DNA replication initiation zones, highlighting cohesin-mediated loop anchors as essential determinants of their precise location.

    • Daniel J. Emerson
    • , Peiyao A. Zhao
    •  & Jennifer E. Phillips-Cremins
  • Article |

    The molecular determinants for primer synthesis are identified within the catalytic domain of primase-polymerase enzymes, elucidating the mechanisms underlying initiation of primer synthesis.

    • Arthur W. H. Li
    • , Katerina Zabrady
    •  & Aidan J. Doherty
  • Article |

    Mother cells recycle parental MCMs and simultaneously synthesize nascent MCMs, both of which are inherited by daughter cells, in which the former are preferentially used to form active replisomes and the latter adjust the pace of replisome movement to minimize errors during DNA replication.

    • Hana Sedlackova
    • , Maj-Britt Rask
    •  & Jiri Lukas
  • Article |

    DNA replication in eukaryotes requires the histone variant H2A.Z, which binds the enzyme SUV420H1 to promote the dimethylation of histone H4, in turn recruiting the origin-recognition complex to activate early replication origins.

    • Haizhen Long
    • , Liwei Zhang
    •  & Guohong Li
  • Article |

    A phospho-switch is identified in the shelterin subunit TRF2 that regulates transient recruitment of the RTEL1 helicase to, and release from, telomeres, and provides a narrow window during which RTEL1 can unwind t-loops to facilitate telomere replication.

    • Grzegorz Sarek
    • , Panagiotis Kotsantis
    •  & Simon J. Boulton
  • Article |

    BRCA1–BARD1 has a role in replication fork protection that is mediated by a mechanism of phosphorylation-targeted isomerization of BRCA1 and is independent of the canonical interaction between BRCA1 and PALB2.

    • Manuel Daza-Martin
    • , Katarzyna Starowicz
    •  & Joanna R. Morris
  • Letter |

    In vitro experiments, using purified proteins and an assay that detects DNA unwinding, reveal the mechanism of activation of eukaryotic DNA replication.

    • Max E. Douglas
    • , Ferdos Abid Ali
    •  & John F. X. Diffley
  • Letter |

    When transcription and replication machineries collide on DNA, they can cause mutations to occur in the area near the collision; these mutations are now shown to include two types—duplications/deletions within the transcription unit and base substitutions in the cis-regulatory element of gene expression.

    • T. Sabari Sankar
    • , Brigitta D. Wastuwidyaningtyas
    •  & Jue D. Wang
  • Letter |

    Common fragile sites (CFSs) are difficult-to-replicate regions of eukaryotic genomes that are sensitive to replication stress and that require resolution by the MUS81–EME1 endonuclease to re-initiate POLD3-dependent DNA synthesis in early mitosis; this study defines the specific pathway of events causing the CFS fragility phenotype.

    • Sheroy Minocherhomji
    • , Songmin Ying
    •  & Ian D. Hickson
  • Letter |

    The Tus–Ter termination site of Escherichia coli is not completely efficient in stopping DNA replication, with about half of replisomes bypassing this blockade; here the speed of the replication machinery is shown to determine the outcome of the encounter between the replisome and Tus–Ter.

    • Mohamed M. Elshenawy
    • , Slobodan Jergic
    •  & Samir M. Hamdan
  • Article |

    This study describes a new model of eukaryotic replication termination in which converging leading strands pass each other unhindered and the replicative DNA helicase is unloaded late, after all strands have been ligated.

    • James M. Dewar
    • , Magda Budzowska
    •  & Johannes C. Walter
  • Article |

    Cryo-electron microscopy is used to visualize the double hexamer of the eukaryotic minichromosome maintenance complex (MCM), which is assembled during the G1 phase of DNA replication; two interdigitated hexamers have a central channel that tightly fits a DNA duplex, and the orientation of the tilted single hexamers sheds light on many functional aspects, particularly in the initial origin DNA melting.

    • Ningning Li
    • , Yuanliang Zhai
    •  & Ning Gao
  • Article |

    This study identifies a crucial role for fatty acid oxidation (FAO) in endothelial cells during angiogenesis, and reveals that fatty-acid-derived carbons are used for the de novo synthesis of nucleotides, and hence FAO stimulates vessel sprouting by increasing endothelial cell proliferation.

    • Sandra Schoors
    • , Ulrike Bruning
    •  & Peter Carmeliet
  • Article |

    The crystal structure of the heterohexameric origin recognition complex (ORC), essential for coordinating DNA replication onset in eukaryotes, is resolved at 3.5 Å resolution.

    • Franziska Bleichert
    • , Michael R. Botchan
    •  & James M. Berger
  • Article |

    It has long been a goal to reconstitute eukaryotic DNA replication; here a purified in vitro system from budding yeast containing 16 factors, themselves composed of 42 polypeptides, fulfils the staged process of origin-dependent initiation, including its regulation by kinases.

    • Joseph T. P. Yeeles
    • , Tom D. Deegan
    •  & John F. X. Diffley
  • Letter |

    Next-generation sequencing technology is used to show that the error-prone polymerase θ (Polθ) is needed to promote alternative non-homologous end joining at telomeres, and during chromosomal translocations, while counteracting homologous recombination; inhibition of Polθ represents a potential therapeutic strategy for tumours that have mutations in homology-directed repair genes.

    • Pedro A. Mateos-Gomez
    • , Fade Gong
    •  & Agnel Sfeir
  • Letter |

    In studies in mammalian cells, polymerase theta (Polθ, also known as POLQ) is identified as the polymerase responsible for non-homologous end joining DNA repair; this DNA repair pathway acts in many tumours when homologous recombination is inactivated and the identification of the polymerase responsible may aid the development of new therapeutic approaches.

    • Raphael Ceccaldi
    • , Jessica C. Liu
    •  & Alan D. D’Andrea
  • Article |

    The emRiboSeq sequencing method is used to track polymerase activity genome-wide in vivo; despite Okazaki fragment processing, DNA synthesized by error-prone polymerase-α (Pol-α) is retained in vivo and comprises ∼1.5% of the genome, establishing Pol-α as an important source of genomic variability and providing a mechanism for site-specific variation in nucleotide substitution rates.

    • Martin A. M. Reijns
    • , Harriet Kemp
    •  & Martin S. Taylor
  • Letter
    | Open Access

    A study of DNA replication timing in mouse and human cells reveals that replication domains (domains of the genome which replicate at the same time) share a correlation with topologically associating domains; these results reconcile cell-type-specific sub-nuclear compartmentalization with developmentally stable chromosome domains and offer a unified model for large scale chromosome structure and function.

    • Benjamin D. Pope
    • , Tyrone Ryba
    •  & David M. Gilbert
  • Letter |

    Haematopoietic stem cell (HSC) function is known to degrade with age; here, replication stress is shown to be a potent driver of the functional decline of HSCs during physiological ageing in mice due to decreased expression of mini-chromosome maintenance helicase components and reduced activity of the DNA replication machinery.

    • Johanna Flach
    • , Sietske T. Bakker
    •  & Emmanuelle Passegué
  • Letter |

    Triphosphates of hydrophobic nucleotides d5SICS and dNaM are imported into Escherichia coli by an exogenous algal nucleotide triphosphate transporter and then used by an endogenous polymerase to replicate, and faithfully maintain over many generations of growth, a plasmid containing the d5SICS–dNaM unnatural base pair.

    • Denis A. Malyshev
    • , Kirandeep Dhami
    •  & Floyd E. Romesberg
  • Article |

    In order to find a general treatment for cancer, this study found that MTH1 activity is essential for the survival of transformed cells, and isolated two small-molecule inhibitors of MTH1, TH287 and TH588 — in the presence of these inhibitors, damaged nucleotides are incorporated into DNA only in cancer cells, causing cytotoxicity and eliciting a beneficial response in patient-derived mouse xenograft models.

    • Helge Gad
    • , Tobias Koolmeister
    •  & Thomas Helleday
  • Letter |

    When all origins of replication are deleted from the archaeon Haloferax volcanii, homologous recombination is used to initiate DNA replication and the growth rate is accelerated.

    • Michelle Hawkins
    • , Sunir Malla
    •  & Thorsten Allers
  • Letter |

    This paper demonstrates that the mechanism of break-induced replication (BIR) is significantly different from S-phase replication, as it proceeds via a migrating bubble driven by Pif1 helicase, results in conservative inheritance of newly synthesized DNA, and is inherently mutagenic.

    • Natalie Saini
    • , Sreejith Ramakrishnan
    •  & Anna Malkova
  • Letter |

    The site of collision between two chromosome replication forks can be used to reinitiate replication independent of an active origin, with potentially pathogenic effects.

    • Christian J. Rudolph
    • , Amy L. Upton
    •  & Robert G. Lloyd
  • Letter |

    A mechanism to explain chromosomal instability (CIN) in colorectal cancer is demonstrated; three new CIN-suppressor genes (PIGN, MEX3C and ZNF516) encoded on chromosome 18q are identified, the loss of which leads to DNA replication stress, resulting in structural and numerical chromosome segregation errors, which are shown to be identical to phenotypes seen in CIN cells.

    • Rebecca A. Burrell
    • , Sarah E. McClelland
    •  & Charles Swanton
  • News & Views |

    Single-molecule studies reveal that a ring-like enzyme that encircles and 'slides' along one strand of duplex DNA, separating it from the other strand, overcomes molecular barriers in its path by transiently opening its ring. See Article p.205

    • Michael A. Trakselis
    •  & Brian W. Graham
  • Article |

    Single-molecule and ensemble assays are used to show that large T antigen, the replicative DNA helicase of the simian virus 40 (SV40), unwinds DNA as a single hexamer by steric exclusion and is able to bypass covalent DNA–protein crosslinks.

    • Hasan Yardimci
    • , Xindan Wang
    •  & Johannes C. Walter
  • Letter |

    A new mechanism of chromosomal rearrangement is identified through the observation that broken or collapsed DNA replication forks restarted by homologous recombination have a high propensity for U-turns at short inverted repeats; the error-prone nature of this mechanism is suggested to contribute to gross chromosomal rearrangements and copy-number variations present in cancer and other genomic disorders.

    • Ken’Ichi Mizuno
    • , Izumi Miyabe
    •  & Johanne M. Murray