Article
Biology
Jasmin Philip, Mihkel Ord, Andriele Silva, Shaneen Singh, John F. X. Diffley, Dirk Remus, Mart Loog, Amy E. Ikui
Summary: This study reveals that PP2A(Cdc55) dephosphorylates the N-terminal sites of Cdc6 to release Clb2, while Cdc14 dephosphorylates the C-terminal phospho-degron to stabilize Cdc6 in mitosis. Additionally, the Cdk1 inhibitor Sic1 releases Clb2·Cdk1·Cks1 from Cdc6 to load Mcm2-7 on the chromatin upon mitotic exit. The findings suggest that phosphatases promote pre-RC assembly and origin licensing through the attenuation of different Cdk1-dependent inhibitory mechanisms of Cdc6.
Article
Multidisciplinary Sciences
Jan Marten Schmidt, Ran Yang, Ashish Kumar, Olivia Hunker, Jan Seebacher, Franziska Bleichert
Summary: The coordinated action of multiple replicative helicase loading factors is required for the licensing of replication origins. CDK phosphorylation can inhibit the loading process and prevent DNA re-replication.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Gemma Regan-Mochrie, Timothy Hoggard, Nikhil Bhagwat, Gerard Lynch, Neil Hunter, Dirk Remus, Catherine A. Fox, Xiaolan Zhao
Summary: The study reveals the importance of sumoylation, a posttranslation modification, in regulating chromosome duplication and stability. Hypersumoylation and hyposumoylation of yeast ORC were found to have opposite effects on ORC activity and origin function. Proper levels of ORC sumoylation are necessary for genome stability and cell fitness.
GENES & DEVELOPMENT
(2022)
Editorial Material
Biochemistry & Molecular Biology
Gergely Rona, Michele Pagano
Summary: Cells prevent rereplication by avoiding licensing of neosynthesized DNA. In this study published in Molecular Cell, Ratnayeke et al. (2022)(1) demonstrate that the licensing factor CDT1 inhibits CMG helicase progression at replication forks by suppressing DNA elongation before its degradation.
Article
Cell Biology
Caitlin Connolly, Saori Takahashi, Hisashi Miura, Ichiro Hiratani, Nick Gilbert, Anne D. Donaldson, Shin-Ichiro Hiraga
Summary: The organization of chromatin is important for chromosomal activities. SAF-A protein plays a crucial role in promoting DNA replication and maintaining its progression. Depletion of SAF-A results in reduced origin licensing, inconsistent replication forks, and changes in replication timing.
JOURNAL OF CELL SCIENCE
(2022)
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
Biochemistry & Molecular Biology
Zeynep Tarcan, Divyasree Poovathumkadavil, Aggeliki Skagia, Agnieszka Gambus
Summary: Complex cellular processes depend on the assembly and disassembly of multiprotein complexes. While the molecular mechanism for assembly of the replisome is understood, little is known about its disassembly at replication termination. In this study, the authors identified the p97 cofactors Ubxn7 and Faf1 as regulators of replisome disassembly. They found that Ubxn7 interacts with both Cul2 (Lrr1) and p97 to facilitate efficient replisome disassembly. This study provides new insights into the regulation of replisome disassembly in vertebrates.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Liu Mei, Katarzyna M. Kedziora, Eun-Ah Song, Jeremy E. Purvis, Jeanette Gowen Cook
Summary: In this study, the authors quantified the dynamics and distribution of DNA replication origin licensing for the first time. They found that the loading rate of MCM complexes is different between euchromatin and heterochromatin. The study also revealed the consequences of heterochromatin licensing dynamics, leading to DNA damage accumulation in subsequent phases. Therefore, the length of G1 phase is critical for sufficient MCM loading, genome duplication, and genome stability.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Nalin Ratnayeke, Yasemin Baris, Mingyu Chung, Joseph T. P. Yeeles, Tobias Meyer
Summary: Human cells license origins of replication in G1, but must stop licensing before DNA synthesis to prevent re-replication. The degradation of licensing factor CDT1 by E3 ubiquitin ligase CRL4Cdt2 is delayed after origin firing, so cells prevent re-replication by inhibiting DNA synthesis through CDT1, and DNA synthesis begins once CDT1 is degraded.
Article
Multidisciplinary Sciences
Humberto Sanchez, Kaley McCluskey, Theo van Laar, Edo van Veen, Filip M. Asscher, Belen Solano, John F. X. Diffley, Nynke H. Dekker
Summary: The study demonstrates the dynamics of the origin recognition complex and subsequent intermediates leading to the loading of an MCM helicase onto DNA using single-molecule optical trapping and confocal microscopy. ORC is shown to be a mobile protein that diffuses rapidly along DNA, with recruitment of MCM molecules in a ORC- and Cdc6-dependent way resulting in slow-moving ORC-MCM intermediates and rapidly scanning MCMs on DNA.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Matthew W. Parker, Jonchee A. Kao, Alvin Huang, James M. Berger, Michael R. Botchan
Summary: Researchers demonstrate that phase separation is driven by a synergy between electrostatic DNA-bridging interactions and hydrophobic inter-IDR contacts, dependent on sequence composition but not order. These interactions are resistant to 1,6-hexanediol and independent of aromaticity, revealing distinct mechanisms underlying condensate formation and specificity in different phase-separating systems.
Article
Multidisciplinary Sciences
Annie Zhang, Larry J. Friedman, Jeff Gelles, Stephen P. Bell
Summary: This study reveals the importance of dynamic protein-DNA interactions in ensuring bidirectional DNA replication during origin licensing. The results show that ORC can ensure head-to-head helicase alignment by sequentially loading Mcm2-7, and that controlled DNA sliding allows ORC to access secondary DNA-binding sites at different locations relative to the initial binding site.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
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
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
Pharmacology & Pharmacy
Konstantina Kaplani, Stamatina Koutsi, Vasileios Armenis, Foteini G. Skondra, Nickolas Karantzelis, Spyridon Champeris Tsaniras, Stavros Taraviras
ADVANCED DRUG DELIVERY REVIEWS
(2018)
Article
Oncology
Nikolaos I. Kanellakis, Anastasios D. Giannou, Mario A. A. Pepe, Theodora Agalioti, Dimitra E. Zazara, Ioanna Giopanou, Ioannis Psallidas, Magda Spella, Antonia Marazioti, Kristina A. M. Arendt, Anne Sophie Lamort, Spyridon Champeris Tsaniras, Stavros Taraviras, Helen Papadaki, Ioannis Lilis, Georgios T. Stathopoulos
Article
Neurosciences
Gonzalo Ortiz-Alvarez, Marie Daclin, Asm Shihavuddin, Pauline Lansade, Aurelien Fortoul, Marion Faucourt, Solene Clavreul, Maria-Eleni Lalioti, Stavros Taraviras, Simon Hippenmeyer, Jean Livet, Alice Meunier, Auguste Genovesio, Nathalie Spassky
Article
Cell Biology
Maria-Eleni Lalioti, Marina Arbi, Ioannis Loukas, Konstantina Kaplani, Argyro Kalogeropoulou, Georgia Lokka, Christina Kyrousi, Athanasia Mizi, Theodore Georgomanolis, Natasa Josipovic, Dimitrios Gkikas, Vladimir Benes, Panagiotis K. Politis, Argyris Papantonis, Zoi Lygerou, Stavros Taraviras
JOURNAL OF CELL SCIENCE
(2019)
Review
Biochemistry & Molecular Biology
Michalis Petropoulos, Spyridon Champeris Tsaniras, Stavros Taraviras, Zoi Lygerou
TRENDS IN BIOCHEMICAL SCIENCES
(2019)
Article
Neurosciences
Maria-Eleni Lalioti, Konstantina Kaplani, Georgia Lokka, Theodore Georgomanolis, Christina Kyrousi, Weilai Dong, Ashley Dunbar, Evangelia Parlapani, Eleni Dannianidou, Nathalie Spassky, Kristopher T. Kahle, Argyris Papantonis, Zoi Lygerou, Stavros Taraviras
Article
Rheumatology
Ioannis Antonopoulos, Dimitrios Daoussis, Maria-Eleni Lalioti, Theodora E. Markatseli, Alexandros A. Drosos, Stavros Taraviras, Andrew P. Andonopoulos, Stamatis-Nick C. Liossis
RHEUMATOLOGY INTERNATIONAL
(2019)
Article
Cell Biology
George Karkoulias, Katie A. McCrink, Jennifer Maning, Celina M. Pollard, Victoria L. Desimine, Nicholas Patsouras, Miltiades Psallidopoulos, Stavros Taraviras, Anastasios Lymperopoulos, Christodoulos Flordellis
CELLULAR SIGNALLING
(2020)
Article
Biochemical Research Methods
Maria Mougkogianni, Argyro Kalogeropoulou, Nickolaos Nikiforos Giakoumakis, Zoi Lygerou, Stavros Taraviras
Summary: Recruitment of the MCM complex on DNA replication origins is critical for faithful genome duplication, with aberrant licensing linked to cancer and neurodevelopmental diseases. An optimized approach for qualitative and quantitative analysis of DNA-bound MCMs in the developing mouse cortex has been developed, offering innovative insights into in vivo research on origin licensing.
Article
Oncology
Spyridon Champeris Tsaniras, George J. Delinasios, Michalis Petropoulos, Andreas Panagopoulos, Athanasios K. Anagnostopoulos, Maria Villiou, Dimitrios Vlachakis, Vasiliki Bravou, Georgios T. Stathopoulos, Stavros Taraviras
CANCER GENOMICS & PROTEOMICS
(2019)
Review
Cell Biology
Argyro Kalogeropoulou, Zoi Lygerou, Stavros Taraviras
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2019)
Article
Biology
Akiyo Hayashi, Nickolaos Nikiforos Giakoumakis, Tatjana Heidebrecht, Takashi Ishii, Andreas Panagopoulos, Christophe Caillat, Michiyo Takahara, Richard G. Hibbert, Naohiro Suenaga, Magda Stadnik-Spiewak, Tatsuro Takahashi, Yasushi Shiomi, Stavros Taraviras, Eleonore von Castelmur, Zoi Lygerou, Anastassis Perrakis, Hideo Nishitani
LIFE SCIENCE ALLIANCE
(2018)
Meeting Abstract
Pathology
S. Nikou, P. Chadla, T. Kalliakoudas, S. Taraviras, V. Bravou
Review
Biochemistry & Molecular Biology
Marina Arbi, Dafni-Eleftheria Pefani, Stavros Taraviras, Zoi Lygerou
Article
Oncology
Dimitrios Tsoumas, Sofia Nikou, Efstathia Giannopoulou, Spyridon Champeris Tsaniras, Chaido Sirinian, Ioannis Maroulis, Stavros Taraviras, Vassiliki Zolota, Haralabos P. Kalofonos, Vasiliki Bravou
CANCER GENOMICS & PROTEOMICS
(2018)