Article
Biology
Pedro Ferreira, Luis Sanchez-Pulido, Anika Marko, Chris P. Ponting, Dominik Boos
Summary: The faithful duplication of the genome requires controlled replication origin firing. The proteins Treslin/TICRR and its yeast counterpart Sld3 play a crucial role in regulating the firing of replication origins. A revised domain architecture model of Treslin/TICRR is proposed, revealing a conserved beta-barrel fold in the middle domain (M domain) shared by Treslin/TICRR and Sld3. It is found that Treslin/Sld3 and MTBP/Sld7 engage in homotypic interactions similar to the dimerization of Ku70-Ku80. Mutants of the Treslin/TICRR domain indicate the importance of all Sld3-core domains and the non-conserved terminal domains during origin firing in human cells.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Rebecca L. Kelly, Amelia M. Huehls, Annapoorna Venkatachalam, Catherine J. Huntoon, Yuichi J. Machida, Larry M. Karnitz
Summary: Replication stress impedes DNA polymerase progression and regulates the interaction between Treslin and TopBP1 through Chk1. This study demonstrates that Chk1 regulates Treslin-TopBP1 interaction through multiple mechanisms, including reducing CDK activity and direct phosphorylation of Treslin, further advancing our understanding of Treslin regulation during the intra-S phase checkpoint.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Gijs Zonderland, Riccardo Vanzo, Sampath Amitash, Elena Martin-Doncel, Fabian Coscia, Andreas Mund, Mads Lerdrup, Jan Benada, Dominik Boos, Luis Toledo
Summary: In contrast to existing models, the TRESLIN-MTBP complex can prevent premature entry into G2 independently of ATR/CHK1 kinases in early S-phase. It acts as a monitoring system that checks the activation of replication forks and senses the rate of origin firing to prevent premature entry into G2.
Article
Cell Biology
Gonzalo Ortiz-Alvarez, Aurelien Fortoul, Ayush Srivastava, Matthieu X. Moreau, Benoit Bouloudi, Caroline Mailhes-Hamon, Nathalie Delgehyr, Marion Faucourt, Mathieu Bahin, Corinne Blugeon, Marielle Breau, Vincent Geli, Frederic Causeret, Alice Meunier, Nathalie Spassky
Summary: Multiciliated ependymal cells and adult neural stem cells, regulated by Geminin family members, play crucial roles in brain homeostasis. DNA damage response and cell cycle slowdown/arrest are important for the differentiation of ependymal cells initiated by GemC1.
Article
Multidisciplinary Sciences
Hanae Omiya, Shima Yamaguchi, Tomoyuki Watanabe, Takaaki Kuniya, Yujin Harada, Daichi Kawaguchi, Yukiko Gotoh
Summary: The differentiation of ependymal cells in the lateral ventricles is controlled by the bone morphogenetic protein (BMP) signaling pathway, which suppresses the differentiation from neural progenitor cells to ependymal cells.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Oana N. Antonescu, Andreas Rasmussen, Nicole A. M. Damm, Ditte F. Heidemann, Roman Popov, Alexander Nesterov-Mueller, Kristoffer E. Johansson, Jakob R. Winther
Summary: A novel platform for functional analysis of leave-one-out split fluorescent proteins (LOO-FPs) was established and validated, with over 12,000 variants of β-strand split fragment screened using high-density peptide microarrays. The effects of peptide length and different linkers on solid support, as well as amino acid substitutions on each position, were studied. Results indicate that the signal intensity on the peptide microarray faithfully reflects the binding affinity between split fragments, with a 9-fold higher affinity peptide identified.
Article
Genetics & Heredity
Seiji Tanaka
Summary: DNA replication in eukaryotes involves a multi-step process with key reactions including helicase loading, activation, and nascent DNA synthesis. While chromatin regulatory factors have been studied in licensing and elongation, their role in the firing reaction remains unclear. In yeast, overexpression of 3-7-45 leads to untimely activation of replication origins, with interactions between Sld3 and Esa1 playing a crucial role in this process. These results highlight the novel regulatory role of Sld3-Esa1 interaction in DNA replication.
Article
Immunology
Manfred Fliegauf, Renate Krueger, Sophie Steiner, Leif Gunnar Hanitsch, Sarah Buechel, Volker Wahn, Horst von Bernuth, Bodo Grimbacher
Summary: In a German family, a previously uncharacterized heterozygous NFKB1 missense variant was identified in four members diagnosed with common variable immunodeficiency (CVID). The clinical phenotypes varied among affected family members but supported a disease mechanism provoked by a p105/p50 (haplo)insufficient condition in the presence of the pathogenic NFKB1 variant.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Materials Science, Multidisciplinary
Emanuele Rossi, Hongzhi Zhang, Santiago J. Garcia, Johan Bijleveld, Timo G. Nijland, Oguzhan Copuroglu, Rob B. Polder, Branko Savija
Summary: The study investigated the elastic modulus of naturally-generated chloride-induced corrosion products in different concrete mixes. Microstructural characterization was carried out using nano-indentation, electron microscopy, and Raman spectroscopy. The results showed that the corrosion products consist mainly of a goethite matrix with portions of maghemite, and the elastic modulus varied between 80-100 GPa.
Article
Multidisciplinary Sciences
Hau B. Nguyen, Thomas C. Terwilliger, Geoffrey S. Waldo
Summary: Research has shown the utility of split fluorescent proteins for large scale protein labeling in cells, but efficient split fluorescent proteins that do not cross-react are needed for multiplexing experiments. The newly proposed split ccGFP from C. californica complements up to threefold faster compared to the original A. victoria split GFP, enabling multiplexed labeling with existing A. victoria split YFP and CFP.
SCIENTIFIC REPORTS
(2021)
Article
Gastroenterology & Hepatology
Sergio Rodriguez-Tajes, Maria Garcia-Eliz, Arantxa Caballero Marcos, Isabel Campos Varela, Alba Cachero Ros, Carmelo Loinaz, Miguel a. Gomez Bravo, Manuel Rodriguez-Peralvarez, Emilio Fabrega, Maria L. Gonzalez Dieguez, Carmen Vinaixa, Jose M. Pascasio, Inmaculada Fernandez Vazquez, Carme Baliellas, Lluis Castells, Magdalena Salcedo, Martin Prieto, Gonzalo Crespo, Sabela Lens, Xavier Forns
Summary: This study analysed the real-life clinical practice of HBIG usage in HDV-related liver transplant patients and found that limited use of HBIG can effectively prevent HBV/HDV recurrence, especially when high-barrier NAs are used.
LIVER INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Taylor B. Dolberg, Anthony T. Meger, Jonathan D. Boucher, William K. Corcoran, Elizabeth E. Schauer, Alexis N. Prybutok, Srivatsan Raman, Joshua N. Leonard
Summary: Splitting bioactive proteins into conditionally reconstituting fragments is powerful, but split proteins often exhibit high propensity to reconstitute, limiting their utility. This new technology, based on computational design strategy and experimental evaluation of mutants, can effectively address split protein design challenges.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Diletta Ciardo, Olivier Haccard, Hemalatha Narassimprakash, David Cornu, Ida Chiara Guerrera, Arach Goldar, Kathrin Marheineke
Summary: This study demonstrates that Plk1 plays a crucial role in regulating replication origin firing during the non-challenged S phase through interactions with various factors. By analyzing the effects of Plk1 depletion on replication fork density and initiation frequency, as well as its interaction with Rif1 and other firing factors, the study provides insights into how Plk1 controls the activation of origins at the level of large chromatin domains in vertebrates.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Mami Oikawa, Hisato Kobayashi, Makoto Sanbo, Naoaki Mizuno, Kenyu Iwatsuki, Tomoya Takashima, Keiko Yamauchi, Fumika Yoshida, Takuya Yamamoto, Takashi Shinohara, Hiromitsu Nakauchi, Kazuki Kurimoto, Masumi Hirabayashi, Toshihiro Kobayashi
Summary: The in vitro generation of germ cells from pluripotent stem cells has significant implications for reproductive medicine and animal breeding. In this study, researchers successfully induced functional primordial germ cell-like cells from rat pluripotent stem cells and generated functional spermatids through transplantation. This research provides insights into the mechanisms of in vitro gametogenesis and has implications for broader applications.
Review
Biology
Seiji Tanaka, Shiho Ogawa
Summary: The activity of replication origins is regulated by firing factors, and dimerization of these factors may contribute to the simultaneous activation of two sets of helicases and thus the efficient assembly of bidirectional replication forks.
Article
Biochemistry & Molecular Biology
Stephen Tutton, Greggory A. Azzam, Nicholas Stong, Olga Vladimirova, Andreas Wiedmer, Jessica A. Monteith, Kate Beishline, Zhuo Wang, Zhong Deng, Harold Riethman, Steven B. McMahon, Maureen Murphy, Paul M. Lieberman
Article
Cell Biology
Jinzhen Guo, Liya Gu, Michael Leffak, Guo-Min Li
Correction
Biochemistry & Molecular Biology
Joanna Barthelemy, Helmut Hanenberg, Michael Leffak
NUCLEIC ACIDS RESEARCH
(2017)
Review
Virology
Shauna A. Marvin
Review
Virology
Zhuo Wang, Zhong Deng, Steve Tutton, Paul M. Lieberman
Article
Multidisciplinary Sciences
Kate Beishline, Olga Vladimirova, Stephen Tutton, Zhuo Wang, Zhong Deng, Paul M. Lieberman
NATURE COMMUNICATIONS
(2017)
Article
Microbiology
Horng-Shen Chen, Alessandra De Leo, Zhuo Wang, Andrew Kerekovic, Robert Hills, Paul M. Lieberman
Article
Biochemistry & Molecular Biology
Sumeet Poudel, Jianhong Yao, Michael G. Kemp, Michael Leffak
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Todd W. Lewis, Joanna R. Barthelemy, Elizabeth L. Virts, Felicia M. Kennedy, Rujuta Y. Gadgil, Constanze Wiek, Rene M. Linka, Feng Zhang, Paul R. Andreassen, Helmut Hanenberg, Michael Leffak
NUCLEIC ACIDS RESEARCH
(2019)
Article
Multidisciplinary Sciences
Jaewoo Choi, James D. Phelan, George W. Wright, Bjoern Haeupl, Da Wei Huang, Arthur L. Shaffer, Ryan M. Young, Zhuo Wang, Hong Zhao, Xin Yu, Thomas Oellerich, Louis M. Staudt
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
Rujuta Yashodhan Gadgil, Eric J. Romer, Caitlin C. Goodman, S. Dean Rider Jr, French J. Damewood, Joanna R. Barthelemy, Kazuo Shin-ya, Helmut Hanenberg, Michael Leffak
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
S. Dean Rider, Rujuta Yashodhan Gadgil, David C. Hitch, French J. Damewood, Nathen Zavada, Matilyn Shanahan, Venicia Alhawach, Resha Shrestha, Kazuo Shin-ya, Michael Leffak
Summary: This article investigates the impact of G4-prone structures on genome stability. The results show that ligand stabilization of G4 structures leads to deletions of the G4 consensus sequence and kilobase deletions spanning the G4 and ectopic sites. Furthermore, DNA double-strand breaks at the ectopic site are dependent on the nuclease Mus81. In addition, both the H3 and G4 non-B conformation DNAs exhibit genomic instability, but they respond differently to endogenous replication stress.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Stanley Dean Rider Jr, French J. J. Damewood, Rujuta Yashodhan Gadgil, David C. C. Hitch, Venicia Alhawach, Resha Shrestha, Matilyn Shanahan, Nathen Zavada, Michael Leffak
Summary: Unbiased genetic screens using a lentiviral shRNA library identified genes that suppress break-induced mutagenesis in human cells with fragile non-B DNA. These genes have roles in DNA replication and repair, chromatin modification, responses to ionizing radiation, and replication fork-associated proteins. Novel loci implicated in BIR were also identified. Knockdown of selected candidates increased the frequency of nucleoside analog resistance and DNA rearrangements near the non-B DNA.
Article
Biochemistry & Molecular Biology
Michael Leffak
Article
Biochemistry & Molecular Biology
R. Gadgil, J. Barthelemy, T. Lewis, M. Leffak
BIOPHYSICAL CHEMISTRY
(2017)