Article
Biochemistry & Molecular Biology
Thomas A. Guilliam, Joseph T. P. Yeeles
Summary: The study shows that a yeast replisome is inherently tolerant to the oxidative lesion Tg, efficiently bypassing leading-strand Tg even in the absence of TLS machinery. A switch from Pol epsilon to Pol delta after helicase-polymerase uncoupling promotes rapid, efficient, and error-free lesion bypass at physiological nucleotide levels. Replicase switching may facilitate continued leading-strand synthesis when Pol delta is more effective at bypassing damage than Pol epsilon.
Article
Biochemistry & Molecular Biology
Jan-Gert Bruning, Kenneth J. Marians
Summary: Collisions between the replisome and RNA polymerases are the main obstacle to DNA replication, which can be overcome by utilizing mRNA transcript as a primer and additional factors. Bypassing the obstacles involves the synthesis of new primers and displacement of the RNA polymerases, while factors such as Rep, Mfd, UvrD, and RNase H facilitate the formation of continuous leading strands for replisome bypass. The length of the obstacle, whether it is co-directional RNA polymerases or R-loops, largely determines the efficiency of bypass for the replisome.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Morgan L. Jones, Yasemin Baris, Martin R. G. Taylor, Joseph T. P. Yeeles
Summary: This study determined the structure of a human replisome containing multiple proteins, revealing their interactions and providing insights into the working mechanism of the replisome and how it maintains smooth replication progression.
Article
Biochemistry & Molecular Biology
Jan-Gert Bruening, Kenneth J. Marians
Summary: Collisions between the replisome and RNA polymerases are the main obstacle to DNA replication. Utilization of mRNA transcripts as primers helps overcome co-directional collisions. The process involves synthesizing new primers downstream of the RNA polymerases to facilitate leading-strand synthesis during bypass.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Microbiology
Nora Halgasova, Rachel Javorova, Lucia Bocanova, Daniela Krajcikova, Jacob A. Bauer, Gabriela Bukovska
Summary: The bacteriophage phiBP contains putative replisome organizer, helicase loader, and beta clamp that may play a role in DNA replication. Bioinformatics analysis found that the phiBP replisome organizer belongs to a newly identified family of initiator proteins. Recombinant proteins gpRO-HC and gpRO-HCK8A, with a lysine to alanine substitution at position 8, were prepared and studied. gpRO-HC showed low ATPase activity, regardless of DNA presence, while the mutant demonstrated significantly higher ATPase activity. gpRO-HC bound to both single- and double-stranded DNA substrates, forming higher oligomers composed of about 12 subunits. This study provides valuable information on phage initiator proteins involved in DNA replication in low GC Gram-positive bacteria.
MICROBIOLOGICAL RESEARCH
(2023)
Review
Cell Biology
Marina A. Bellani, Althaf Shaik, Ishani Majumdar, Chen Ling, Michael M. Seidman
Summary: The replication apparatus faces challenges in duplicating the genome, particularly when encountering covalent DNA adducts on the leading template strand. The helicase, a key component of the replication machinery, is responsible for unwinding DNA and coming into contact with the adducts. Recent studies have shown that the helicase is able to tolerate larger adducts than previously believed.
Article
Multidisciplinary Sciences
Dillon B. Nye, Nathan A. Tanner
Summary: Recent advances in next generation sequencing technologies have made it possible to read DNA molecules hundreds of kilobases in length. This has motivated the development of DNA amplification methods capable of producing long amplicons. In this study, the researchers investigated strand-displacement amplification reactions using the T7 replisome, a multiprotein complex involved in DNA replication. They utilized Oxford Nanopore long-read sequencing technology to gain insight into the reaction mechanism. The results revealed chimeric DNA reads and a connection between template switching and polymerase exonuclease activity.
Article
Biology
Po Jui Chen, Anna B. McMullin, Bryan J. Visser, Qian Mei, Susan M. Rosenberg, David Bates
Summary: In bacteria, sister replisomes are functionally interdependent and remain colocalized throughout replication. Our study reveals the crucial role of physical association between sister replisomes in ensuring an efficient and uninterrupted replication program.
Article
Biochemistry & Molecular Biology
Thanh Thi Le, Johanna Ainsworth, Cristian Polo Rivera, Thomas Macartney, Karim P. M. Labib
Summary: Cullin ubiquitin ligases drive CMG-MCM7 ubiquitylation in human cells, converting the helicase into a substrate for p97 unfoldase.
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Kyle B. Vrtis, James M. Dewar, Gheorghe Chistol, R. Alex Wu, Thomas G. W. Graham, Johannes C. Walter
Summary: Research has shown that collisions between the replicative CMG helicase and nicks in DNA templates can lead to different forms of double-strand breaks, causing replisome disassembly.
Review
Biochemistry & Molecular Biology
Thomas A. Guilliam
Summary: The eukaryotic replisome encounters obstacles such as damaged and structured DNA during replication, but various mechanisms exist to overcome these hurdles, maintain progression, and prevent fork collapse. Recent advances in structural, biochemical, and single-molecule approaches have enhanced our understanding of the replisome's architecture, response to impediments, and DNA damage tolerance mechanisms.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Genetics & Heredity
Liana Goehring, Tony T. Huang, Duncan J. Smith
Summary: This review focuses on the conflicts between transcription and replication, known as transcription-replication conflicts (TRCs), and their impact on genome stability. Recent studies on the genomic locations of TRCs and the mechanisms to prevent or resolve them shed light on how cells regulate and protect DNA during replication and transcription.
ANNUAL REVIEW OF GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Yoshitami Hashimoto, Kota Sadano, Nene Miyata, Haruka Ito, Hirofumi Tanaka
Summary: DONSON is a novel initiator protein essential for CMG helicase assembly in vertebrates, as demonstrated by experiments in a Xenopus cell-free system. DONSON interacts with GINS and Pol ε to promote replisome assembly, and its chromatin association during replication initiation requires the pre-replicative complex, TopBP1, and kinase activities of S-CDK and DDK.
Review
Cell Biology
Janne J. M. van Schie, Job de Lange
Summary: The cohesin complex plays a vital role in accurate chromosome segregation by pairing sister chromatids and assisting in error-free DNA replication. The processes of replisome progression and establishment of sister chromatid cohesion are closely linked. Understanding how key factors in DNA replication and cohesion establishment cooperate under normal and stressed conditions is crucial for studying genome stability.
Review
Biochemistry & Molecular Biology
Rebeca Bocanegra, Ismael G. A. Plaza, Carlos R. Pulido, Borja Ibarra
Summary: The study reveals that the replisome machinery is stochastic, versatile, and highly dynamic, with transient protein-protein and protein-DNA interactions playing a key role in robust DNA replication.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Ineke Brouwer, Tommaso Moschetti, Andrea Candelli, Edwige B. Garcin, Mauro Modesti, Luca Pellegrini, Gijs J. L. Wuite, Erwin J. G. Peterman
Article
Cell Biology
Harveer Dev, Ting-Wei Will Chiang, Chloe Lescale, Inge de Krijger, Alistair G. Martin, Domenic Pilger, Julia Coates, Matylda Sczaniecka-Clift, Wenming Wei, Matthias Ostermaier, Mareike Herzog, Jonathan Lam, Abigail Shea, Mukerrem Demir, Qian Wu, Fengtang Yang, Beiyuan Fu, Zhongwu Lai, Gabriel Balmus, Rimma Belotserkovskaya, Violeta Serra, Mark J. O'Connor, Alejandra Bruna, Petra Beli, Luca Pellegrini, Carlos Caldas, Ludovic Deriano, Jacqueline J. L. Jacobs, Yaron Galanty, Stephen P. Jackson
NATURE CELL BIOLOGY
(2018)
Article
Multidisciplinary Sciences
Jiangyu Yan, Sandro Holzer, Luca Pellegrini, Stephen D. Bell
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Editorial Material
Biochemistry & Molecular Biology
Luca Pellegrini
Article
Biochemistry & Molecular Biology
Cecile Evrin, Joseph D. Maman, Aurora Diamante, Luca Pellegrini, Karim Labib
Article
Biochemistry & Molecular Biology
Sandro Holzer, Neil J. Rzechorzek, Isobel R. Short, Michael Jenkyn-Bedford, Luca Pellegrini, Mairi L. Kilkenny
ACS CHEMICAL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Daniel Bollschweiler, Laura Radu, Luay Joudeh, Juergen M. Plitzko, Robert M. Henderson, Ioanna Mela, Luca Pellegrini
Article
Biochemistry & Molecular Biology
Neil J. Rzechorzek, Steven W. Hardwick, Vincentius A. Jatikusumo, Dimitri Y. Chirgadze, Luca Pellegrini
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Leticia K. Lerner, Sandro Holzer, Mairi L. Kilkenny, Sasa Svikovic, Pierre Murat, Davide Schiavone, Cara B. Eldridge, Alice Bittleston, Joseph D. Maman, Dana Branzei, Katherine Stott, Luca Pellegrini, Julian E. Sale
Article
Multidisciplinary Sciences
Gabriel Tarrason Risa, Fredrik Hurtig, Sian Bray, Anne E. Hafner, Lena Harker-Kirschneck, Peter Faull, Colin Davis, Dimitra Papatziamou, Delyan R. Mutavchiev, Catherine Fan, Leticia Meneguello, Andre Arashiro Pulschen, Gautam Dey, Sian Culley, Mairi Kilkenny, Diorge P. Souza, Luca Pellegrini, Robertus A. M. de Bruin, Ricardo Henriques, Ambrosius P. Snijders, Andela Saric, Ann-Christin Lindas, Nicholas P. Robinson, Buzz Baum
Article
Biochemistry & Molecular Biology
C. R. Morton, N. J. Rzechorzek, J. D. Maman, M. Kuramochi, H. Sekiguchi, R. Rambo, Y. C. Sasaki, O. R. Davies, L. Pellegrini
Summary: This study presents an atomic model for the three-dimensional architecture of human CtIP, revealing its critical role in DNA repair through a multi-disciplinary approach. The data show that CtIP adopts a dimer-of-dimers structure and the zinc-binding motif in the N-terminus alters the coiled-coil structure, affecting CtIP's interactions with DNA. These results provide a structural basis for understanding CtIP's function in DNA DSB repair.
Article
Biochemistry & Molecular Biology
Mairi L. Kilkenny, Charlotte E. Veale, Amir Guppy, Steven W. Hardwick, Dimitri Y. Chirgadze, Neil J. Rzechorzek, Joseph D. Maman, Luca Pellegrini
Summary: Research on the mechanisms of SARS-CoV-2 infection suggests that the virus can disrupt the host immune response by interacting with key host proteins involved in DNA replication.
Article
Multidisciplinary Sciences
Robert Appleby, Daniel Bollschweiler, Dimitri Y. Chirgadze, Luay Joudeh, Luca Pellegrini
Summary: In this study, the researchers investigated the role of RAD51 in homologous recombination. They found that ATP binding to RAD51 promotes its folding into a conformation that allows DNA binding. The presence of a second metal ion at the ATP-binding site explains how RAD51 regulates its interaction with DNA. Loss of the second metal ion upon ATP hydrolysis weakens the stability of RAD51 filament and contributes to its disassembly.
Article
Biochemistry & Molecular Biology
Duncan E. Scott, Nicola J. Francis-Newton, May E. Marsh, Anthony G. Coyne, Gerhard Fischer, Tommaso Moschetti, Andrew R. Bayly, Timothy D. Sharpe, Kalina T. Haas, Lorraine Barber, Chiara R. Valenzano, Rajavel Srinivasan, David J. Huggins, Miyoung Lee, Amy Emery, Bryn Hardwick, Matthias Ehebauer, Claudio Dagostin, Alessandro Esposito, Luca Pellegrini, Trevor Perrior, Grahame McKenzie, Tom L. Blundell, Marko Hyvonen, John Skidmore, Ashok R. Venkitaraman, Chris Abell
Summary: The study identifies CAM833 as an orthosteric inhibitor of RAD51:BRC, which affects DNA repair and potentiates cell death induced by DNA damage, working in coordination with PARP1 inhibitors to suppress growth in BRCA2-wildtype cells.
CELL CHEMICAL BIOLOGY
(2021)