Article
Multidisciplinary Sciences
Sumedha Agashe, Chinnu Rose Joseph, Teresa Anne Clarisse Reyes, Demis Menolfi, Michele Giannattasio, Anja Waizenegger, Barnabas Szakal, Dana Branzei
Summary: The study reveals that Smc5/6 acts together with Top3 within the STR complex to regulate the DNA processing activities of Sgs1 and Top3, maintaining genome structural integrity and mediating DNA replication completion.
NATURE COMMUNICATIONS
(2021)
Review
Genetics & Heredity
Fang Ji, Xinli Zhu, Hongwei Liao, Liujian Ouyang, Yingfei Huang, Madiha Zahra Syeda, Songmin Ying
Summary: This review provides an update on the research progress of common fragile sites (CFSs), including mapping and sequencing techniques, as well as hypotheses on the fragility origin of CFSs. By analyzing the locations, sequences, and replication/transcription of CFSs, this review presents the latest research status of CFSs and potentially offers a new framework for future CFS research.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Jayaraju Dheekollu, Andreas Wiedmer, Kasirajan Ayyanathan, Julianna S. Deakyne, Troy E. Messick, Paul M. Lieberman
Summary: This study reveals that EBNA1 forms cell cycle-dependent DNA crosslinks with the EBV origin of plasmid replication and the tyrosine 518 residue is essential for this process. These crosslinks and single-strand cleavage are critical for replication termination and viral episome maintenance.
Article
Geosciences, Multidisciplinary
Lisa J. Beck, Nina Sarnela, Heikki Junninen, Clara J. M. Hoppe, Olga Garmash, Federico Bianchi, Matthieu Riva, Clemence Rose, Otso Perakyla, Daniela Wimmer, Oskari Kausiala, Tuija Jokinen, Lauri Ahonen, Jyri Mikkila, Jani Hakala, Xu-Cheng He, Jenni Kontkanen, Klara K. E. Wolf, David Cappelletti, Mauro Mazzola, Rita Traversi, Chiara Petroselli, Angelo P. Viola, Vito Vitale, Robert Lange, Andreas Massling, Jakob K. Nojgaard, Radovan Krejci, Linn Karlsson, Paul Zieger, Sehyun Jang, Kitack Lee, Ville Vakkari, Janne Lampilahti, Roseline C. Thakur, Katri Leino, Juha Kangasluoma, Ella-Maria Duplissy, Erkki Siivola, Marjan Marbouti, Yee Jun Tham, Alfonso Saiz-Lopez, Tuukka Petaja, Mikael Ehn, Douglas R. Worsnop, Henrik Skov, Markku Kulmala, Veli-Matti Kerminen, Mikko Sipila
Summary: New particle formation in the Arctic atmosphere is influenced by different factors at different Arctic sites, such as sulfuric acid and methane sulfonic acid contributing to secondary aerosol formation in Svalbard. Understanding these processes is crucial for understanding their impact on cloud properties and Arctic amplification.
GEOPHYSICAL RESEARCH LETTERS
(2021)
Review
Biochemistry & Molecular Biology
Constanze Pentzold, Miriam Kokal, Stefan Pentzold, Anja Weise
Summary: Chromosomal fragile sites, positioned in the interphase nucleus with anchoring points at the nuclear lamina, exhibit fragility in mitosis but actually start in interphase, influencing genomic integrity and sustaining cellular diversity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Cell Biology
Devon M. Fitzgerald, Susan M. Rosenberg
Summary: The Escherichia coli SOS response to DNA damage, discovered by Evelyn Witkin and Miroslav Radman, is the prototypic DNA-damage stress response that upregulates proteins for protection and repair. Similar mechanisms are found across species and contribute to genome instability in human cancer and aging. Bacterial molecular genomic mechanisms can offer insights into universal biology, including in human disease.
Article
Biochemistry & Molecular Biology
Nhung Pham, Zhenxin Yan, Yang Yu, Mosammat Faria Afreen, Anna Malkova, James E. Haber, Grzegorz Ira
Summary: The research demonstrates that mutagenic break-induced replication (BIR) is suppressed at two-ended DNA double-strand breaks (DSBs) by proteins coordinating the usage of two ends of a DSB. Key proteins involved in this suppression include ssDNA annealing proteins Rad52 and Rad59, D-loop unwinding helicase Mph1, and the Mre11-Rad50-Xrs2 complex promoting synchronous resection of DSB ends. Sir2 also plays a role in silencing heterochromatic repair templates to prevent BIR.
Review
Biochemistry & Molecular Biology
Baraah Al Ahmad Nachar, Filippo Rosselli
Summary: DNA replication is a crucial process that requires the coordinated action of multiple proteins to permit, initiate, and progress replication forks. However, there are obstacles that can impede replication fork progression. Cells have developed various mechanisms to protect DNA replication and ensure its completion before entering mitosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Daniel J. Goodall, Katie H. Jameson, Michelle Hawkins, Christian J. Rudolph
Summary: The termination phase of DNA replication is complex, and in Escherichia coli, it involves the formation of a replication fork trap system facilitated by Tus protein binding to ter sites. While this system is present in some bacterial species, it is not a universal feature of bacterial chromosomes. The highly conserved ter sites in E. coli genomes, with slightly more variability in Shigella genomes, suggest the physiological significance of the replication fork trap system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Genetics & Heredity
Ryan P. Barnes, Sanjana A. Thosar, Patricia L. Opresko
Summary: Telomeres present challenges for DNA replication due to their repetitive sequences, non-B DNA structures, and the presence of nucleo-protein t-loops. Telomeres are particularly susceptible to replication stress in cancer cells, resulting in telomere fragility in metaphase cells. One mechanism cells use to cope with replication stress, including at telomeres, is DNA synthesis in mitosis (MiDAS). Although both phenomena are observed in mitotic cells, the relationship between them is poorly understood, but they are both linked by DNA replication stress. In this review, we summarize the regulation of telomere fragility and telomere MiDAS, focusing on the proteins involved in these telomere phenotypes.
Article
Environmental Sciences
Zelin Hou, Fan Mo, Qixing Zhou
Summary: This study investigated the stress response patterns of earthworms in practical petroleum hydrocarbon contamination systems. The results showed that earthworms' cell metabolism shifted under contamination conditions, leading to disruption in epicuticle and cuticle layers. The study also found that petroleum hydrocarbon contamination influenced earthworms' physiological homeostasis indirectly through microbial metabolism regulation.
ENVIRONMENTAL POLLUTION
(2023)
Review
Microbiology
Daniel J. Goodall, Dominika Warecka, Michelle Hawkins, Christian J. Rudolph
Summary: There are two fundamental chromosome replication modes in cellular organisms, including single linear replication in bacteria and multiple linear replication in eukaryotes. Bacteria have a replication fork trap system, which enables more efficient replication termination, while eukaryotes cope with a higher number of replication termination events.
FRONTIERS IN MICROBIOLOGY
(2023)
Review
Genetics & Heredity
Bruce E. Hayward, Karen Usdin
Summary: Fragile X-related disorders are caused by expansion of a CGG-repeat tract in the X-linked FMR1 gene's 5' UTR, including intellectual disability fragile X syndrome. Premutation alleles with 54-200 repeats pose the risk of associated syndromes, while full mutation alleles cause FXS. Expansion and contraction of alleles can lead to mosaic carriers with varied clinical presentations.
Article
Chemistry, Medicinal
Jiao Li, Fumei Zhong, Mingwei Li, Yaqian Liu, Lei Wang, Mingqing Liu, Fudong Li, Jiahai Zhang, Jihui Wu, Yunyu Shi, Zhiyong Zhang, Xiaoming Tu, Ke Ruan, Jia Gao
Summary: This study elucidates the crystal structure of SARS-CoV-2 Mac3, identifies two small-molecule binding sites, and confirms the binding properties and functions of two drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Agriculture, Dairy & Animal Science
Marta Kuchta-Gladysz, Ewa Wojcik, Anna Grzesiakowska, Katarzyna Rymuza, Olga Szeleszczuk
Summary: The paper explores the karyotypes of blue and silver foxes, as well as their hybrids, focusing on A and B chromosome numbers and fragile site frequencies. Genome stability is influenced by Robertsonian translocations in blue foxes and B chromosomes in silver foxes. The study uses fragile sites assay as a biomarker to evaluate genome stability in foxes, with a lower frequency of instabilities observed in healthy individuals. The assay can assist in selecting individuals with stable genomes for breeding, particularly for the conservation of endangered species like the blue fox.
Article
Biochemistry & Molecular Biology
Elizabeth A. Bowling, Jarey H. Wang, Fade Gong, William Wu, Nicholas J. Neill, Ik Sun Kim, Siddhartha Tyagi, Mayra Orellana, Sarah J. Kurley, Rocio Dominguez-Vidana, Hsiang-Ching Chung, Tiffany Y-T Hsu, Julien Dubrulle, Alexander B. Saltzman, Heyuan Li, Jitendra K. Meena, Gino M. Canlas, Srinivas Chamakuri, Swarnima Singh, Lukas M. Simon, Calla M. Olson, Lacey E. Dobrolecki, Michael T. Lewis, Bing Zhang, Ido Golding, Jeffrey M. Rosen, Damian W. Young, Anna Malovannaya, Fabio Stossi, George Miles, Matthew J. Ellis, Lihua Yu, Silvia Buonamici, Charles Y. Lin, Kristen L. Karlin, Xiang H-F Zhang, Thomas F. Westbrook
Summary: This study reveals that mis-spliced RNA can trigger tumor cell death through viral mimicry, where dsRNA-binding proteins recognize mis-spliced RNA and induce antiviral signaling and apoptosis. Additionally, the findings suggest that STTs may activate anti-tumor immune pathways by responding to global aberrations of RNA splicing in cancer.
Article
Multidisciplinary Sciences
Wei Wu, Sarah E. Hill, William J. Nathan, Jacob Paiano, Elsa Callen, Dongpeng Wang, Kenta Shinoda, Niek van Wietmarschen, Jennifer M. Colon-Mercado, Dali Zong, Raffaella De Pace, Han-Yu Shih, Steve Coon, Maia Parsadanian, Raphael Pavani, Hana Hanzlikova, Solji Park, Seol Kyoung Jung, Peter J. McHugh, Andres Canela, Chongyi Chen, Rafael Casellas, Keith W. Caldecott, Michael E. Ward, Andre Nussenzweig
Summary: Defects in DNA repair can lead to neurodevelopmental and neurodegenerative diseases, particularly in long-lived post-mitotic neurons. Neurons accumulate unexpectedly high levels of DNA single-strand breaks at specific sites within the genome, which are repaired by PARP1 and XRCC1-dependent mechanisms. Deficiencies in XRCC1-dependent repair in neurons can lead to increased DNA repair synthesis at neuronal enhancers, while defects in long-patch repair reduce synthesis, potentially contributing to neurodegenerative phenotypes in patients.
Article
Cell Biology
Jacob Paiano, Nicholas Zolnerowich, Wei Wu, Raphael Pavani, Chen Wang, Hongzhi Li, Li Zheng, Binghui Shen, Barry P. Sleckman, Bo-Ruei Chen, Andre Nussenzweig
Summary: The study reveals that Pol alpha reduces resection at DSBs in the presence of 53BP1, but is unable to counteract excessive resection in the absence of 53BP1. This suggests that 53BP1 likely protects DNA ends by inhibiting resection.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Jaclyn M. Einstein, Mark Perelis, Isaac A. Chaim, Jitendra K. Meena, Julia K. Nussbacher, Alexandra T. Tankka, Brian A. Yee, Heyuan Li, Assael A. Madrigal, Nicholas J. Neill, Archana Shankar, Siddhartha Tyagi, Thomas F. Westbrook, Gene W. Yeo
Summary: RNA-binding proteins (RBPs) play crucial roles in post-transcriptional gene expression regulation, and disrupting YTHDF2-dependent mRNA degradation can induce apoptosis in triple-negative breast cancer (TNBC) cells and tumors. Our study identified 57 RBP candidates with distinct functions in supporting MYC-driven oncogenic pathways, highlighting the therapeutic potential of RBPs, especially YTHDF2, in counteracting global mRNA synthesis in MYC-driven breast cancers.
Review
Cell Biology
Devon M. Fitzgerald, Susan M. Rosenberg
Summary: The Escherichia coli SOS response to DNA damage, discovered by Evelyn Witkin and Miroslav Radman, is the prototypic DNA-damage stress response that upregulates proteins for protection and repair. Similar mechanisms are found across species and contribute to genome instability in human cancer and aging. Bacterial molecular genomic mechanisms can offer insights into universal biology, including in human disease.
Article
Biology
Faith C. Fowler, Bo-Ruei Chen, Nicholas Zolnerowich, Wei Wu, Raphael Pavani, Jacob Paiano, Chelsea Peart, Zulong Chen, Andre Nussenzweig, Barry P. Sleckman, Jessica K. Tyler
Summary: This study uncovered extensive DNA end resection at double-strand breaks (DSBs) in G(0) murine and human cells dependent on MRE11 and CtIP. A whole genome CRISPR/Cas9 screen identified the DNA-dependent kinase (DNA-PK) complex as a key factor in promoting DNA end resection in G(0) cells. However, the requirement for DNA-PK in promoting DNA end resection was not observed in proliferating cells at the G(1) or G(2) phase.
Article
Cell Biology
Mohamed E. Ashour, Andrea K. Byrum, Alice Meroni, Jun Xia, Saurabh Singh, Roberto Galletto, Susan M. Rosenberg, Alessandro Vindigni, Nima Mosammaparast
Summary: The primary method for studying DNA replication dynamics, DNA fiber analysis, has limitations in terms of time, bias, and adaptability. In this study, a mass spectrometry-based analysis technique (MS-BAND) was introduced as a rapid and unbiased alternative for quantifying and analyzing DNA replication. MS-BAND accurately detects replication alterations in various cell compartments and has high-throughput capability, making it a potential alternative to the DNA fiber technique.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yin Zhai, P. J. Minnick, John P. Pribis, Libertad Garcia-Villada, P. J. Hastings, Christophe Herman, Susan M. Rosenberg
Summary: Antibiotic resistance is a global health threat caused by new mutations. Antibiotics can induce mutations through stress responses, which reveal environmental cues of mutagenesis and are weak links in mutagenesis networks. Inhibiting these networks can slow the evolution of antibiotic resistance.
Article
Multidisciplinary Sciences
Yin Zhai, John P. Pribis, Sean W. Dooling, Libertad Garcia-Villada, P. J. Minnick, Jun Xia, Jingjing Liu, Qian Mei, Devon M. Fitzgerald, Christophe Herman, P. J. Hastings, Mauro Costa-Mattioli, Susan M. Rosenberg
Summary: Evolution of antibiotic resistance is a global health crisis driven by new mutations. In this study, a network-based strategy was used to identify a drug, dequalinium chloride (DEQ), that inhibits mutagenesis induced by fluoroquinolone antibiotics. DEQ was found to slow down evolution without promoting the growth of DEQ-resistant mutants. The study provides a proof-of-concept strategy for developing drugs to slow down bacterial evolution.