663 results match your criteria cells restart

Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress.

Nat Struct Mol Biol 2021 Jun 10;28(6):487-500. Epub 2021 Jun 10.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Fanconi anemia (FA) is a devastating hereditary disease characterized by bone marrow failure (BMF) and acute myeloid leukemia (AML). As FA-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), ICLs are widely assumed to be the lesions responsible for FA symptoms. Here, we show that FA-mutated cells are hypersensitive to persistent replication stress and that FA proteins play a role in the break-induced-replication (BIR)-like pathway for fork restart. Read More

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SETD2-mediated H3K14 trimethylation promotes ATR activation and stalled replication fork restart in response to DNA replication stress.

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, Shenzhen University School of Medicine, 518055 Shenzhen, China;

Ataxia telangiectasia and Rad3 related (ATR) activation after replication stress involves a cascade of reactions, including replication protein A (RPA) complex loading onto single-stranded DNA and ATR activator loading onto chromatin. The contribution of histone modifications to ATR activation, however, is unclear. Here, we report that H3K14 trimethylation responds to replication stress by enhancing ATR activation. Read More

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Mol Plant 2021 May 29. Epub 2021 May 29.

Centro de Biotecnología y Genómica de Plantas (Universidad Politécnica de Madrid - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria), Pozuelo de Alarcón, 28223, Madrid, Spain. Electronic address:

Post-embryonic organogenesis is critical for plant development. Underground, lateral roots (LR) form the bulk of mature root systems, yet the ontogeny of the LRP is not clear. Here, we use single-cell RNA-seq through the first four stages of LR formation in Arabidopsis. Read More

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Same-day SARS-CoV-2 antigen test screening in an indoor mass-gathering live music event: a randomised controlled trial.

Lancet Infect Dis 2021 May 27. Epub 2021 May 27.

Division of Infectious diseases and Foundation for Fighting AIDS, Infectious Diseases and Promoting Health and Science, University Hospital Germans Trias i Pujol, Badalona, Spain. Electronic address:

Background: The banning of mass-gathering indoor events to prevent SARS-CoV-2 spread has had an important effect on local economies. Despite growing evidence on the suitability of antigen-detecting rapid diagnostic tests (Ag-RDT) for mass screening at the event entry, this strategy has not been assessed under controlled conditions. We aimed to assess the effectiveness of a prevention strategy during a live indoor concert. Read More

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Replication Fork Reversal and Protection.

Front Cell Dev Biol 2021 10;9:670392. Epub 2021 May 10.

Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

During genome replication, replication forks often encounter obstacles that impede their progression. Arrested forks are unstable structures that can give rise to collapse and rearrange if they are not properly processed and restarted. Replication fork reversal is a critical protective mechanism in higher eukaryotic cells in response to replication stress, in which forks reverse their direction to form a Holliday junction-like structure. Read More

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Autism-associated vigilin depletion impairs DNA damage repair.

Mol Cell Biol 2021 May 3. Epub 2021 May 3.

Chromatin and Epigenetics Lab, Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir 190006, India.

Vigilin (Vgl1) is essential for heterochromatin formation, chromosome segregation, mRNA stability and is associated with autism-spectrum disorders and cancer, vigilin, for example, can suppress proto-oncogene c-fms expression in breast cancer. Conserved from yeast to humans, vigilin is an RNA-binding protein with 14 tandemly arranged nonidentical hnRNP K type homology (KH) domains. Here we report that vigilin depletion increased cell sensitivity to cisplatin- or ionizing radiation (IR)-induced cell death and genomic instability due to defective DNA repair. Read More

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FANCM regulates repair pathway choice at stalled replication forks.

Mol Cell 2021 06 20;81(11):2428-2444.e6. Epub 2021 Apr 20.

Department of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA 02215, USA. Electronic address:

Repair pathway "choice" at stalled mammalian replication forks is an important determinant of genome stability; however, the underlying mechanisms are poorly understood. FANCM encodes a multi-domain scaffolding and motor protein that interacts with several distinct repair protein complexes at stalled forks. Here, we use defined mutations engineered within endogenous Fancm in mouse embryonic stem cells to study how Fancm regulates stalled fork repair. Read More

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Live-cell single-molecule tracking highlights requirements for stable Smc5/6 chromatin association in vivo.

Elife 2021 04 16;10. Epub 2021 Apr 16.

Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, United Kingdom.

The essential Smc5/6 complex is required in response to replication stress and is best known for ensuring the fidelity of homologous recombination. Using single-molecule tracking in live fission yeast to investigate Smc5/6 chromatin association, we show that Smc5/6 is chromatin associated in unchallenged cells and this depends on the non-SMC protein Nse6. We define a minimum of two Nse6-dependent sub-pathways, one of which requires the BRCT-domain protein Brc1. Read More

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Controlled Manipulation and Active Sorting of Particles Inside Microfluidic Chips Using Bulk Acoustic Waves and Machine Learning.

Langmuir 2021 04 2;37(14):4192-4199. Epub 2021 Apr 2.

Faculty of Medicine and Health Technology, Tampere University, Korkeakoulunkatu 3, 33720 Tampere, Finland.

Manipulation of cells, droplets, and particles via ultrasound within microfluidic chips is a rapidly growing field, with applications in cell and particle sorting, blood fractionation, droplet transport, and enrichment of rare or cancerous cells, among others. However, current methods with a single ultrasonic transducer offer limited control of the position of single particles. In this paper, we demonstrate closed-loop two-dimensional manipulation of particles inside closed-channel microfluidic chips, by controlling the frequency of a single ultrasound transducer, based on machine-vision-measured positions of the particles. Read More

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Magnetic Nanoparticle-Based Hyperthermia Mediates Drug Delivery and Impairs the Tumorigenic Capacity of Quiescent Colorectal Cancer Stem Cells.

ACS Appl Mater Interfaces 2021 Apr 2;13(14):15959-15972. Epub 2021 Apr 2.

Istituto Italiano di Tecnologia (IIT), via Morego 30, 16163 Genova, Italy.

Cancer stem cells (CSCs) are the tumor cell subpopulation responsible for resistance to chemotherapy, tumor recurrence, and metastasis. An efficient therapy must act on low proliferating quiescent-CSCs (q-CSCs). We here investigate the effect of magnetic hyperthermia (MHT) in combination with local chemotherapy as a dual therapy to inhibit patient-derived colorectal qCR-CSCs. Read More

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Repriming DNA synthesis: an intrinsic restart pathway that maintains efficient genome replication.

Nucleic Acids Res 2021 05;49(9):4831-4847

Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, BN1 9RQ, UK.

To bypass a diverse range of fork stalling impediments encountered during genome replication, cells possess a variety of DNA damage tolerance (DDT) mechanisms including translesion synthesis, template switching, and fork reversal. These pathways function to bypass obstacles and allow efficient DNA synthesis to be maintained. In addition, lagging strand obstacles can also be circumvented by downstream priming during Okazaki fragment generation, leaving gaps to be filled post-replication. Read More

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Knowledge-Guided "Community Network" Analysis Reveals the Functional Modules and Candidate Targets in Non-Small-Cell Lung Cancer.

Cells 2021 Feb 16;10(2). Epub 2021 Feb 16.

Center for Systems Biology, Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.

Non-small-cell lung cancer (NSCLC) represents a heterogeneous group of malignancies that are the leading cause of cancer-related death worldwide. Although many NSCLC-related genes and pathways have been identified, there remains an urgent need to mechanistically understand how these genes and pathways drive NSCLC. Here, we propose a knowledge-guided and network-based integration method, called the node and edge Prioritization-based Community Analysis, to identify functional modules and their candidate targets in NSCLC. Read More

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February 2021

DTFLOW: Inference and Visualization of Single-cell Pseudotime Trajectory Using Diffusion Propagation.

Genomics Proteomics Bioinformatics 2021 Mar 1. Epub 2021 Mar 1.

School of Mathematics, Monash University, Melbourne, VIC 3800, Australia. Electronic address:

One of the major challenges in single-cell data analysis is the determination of cellular developmental trajectories using single-cell data. Although substantial studies have been conducted in recent years, more effective methods are still strongly needed to infer the developmental processes accurately. This work devises a new method, named DTFLOW, for determining the pseudo-temporal trajectories with multiple branches. Read More

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Strategies to Study Dark Growth Deficient or Slower Mutants in Chlamydomonas reinhardtii.

Methods Mol Biol 2021 ;2297:125-140

Key Laboratory of Photobiology, Institute of Botany (CAS), Beijing, China.

Photosynthesis is the most important chemical reaction on the earth, and about 60% of the CO is fixed by algae through photosynthesis. Photosynthetic organisms including algae experience half of the entire life in the dark due to diel cycles, and dark metabolism is critical and necessary for photosynthetic organisms to restart photosynthesis when receiving light again. Briefly, dark metabolism provides necessary materials and energy for restoring photosynthesis, reoxidizes NADH to form NAD, rationally stores photosynthates, and maintains correct redox balance. Read More

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PCNA, a focus on replication stress and the alternative lengthening of telomeres pathway.

DNA Repair (Amst) 2021 Apr 3;100:103055. Epub 2021 Feb 3.

Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, H3A 0C7, Canada; Jewish General Hospital, Lady Davis Institute, Montreal, Quebec, H3T 1E2, Canada. Electronic address:

The maintenance of telomeres, which are specialized stretches of DNA found at the ends of linear chromosomes, is a crucial step for the immortalization of cancer cells. Approximately 10-15 % of cancer cells use a homologous recombination-based mechanism known as the Alternative Lengthening of Telomeres (ALT) pathway to maintain their telomeres. Telomeres in general pose a challenge to DNA replication owing to their repetitive nature and potential for forming secondary structures. Read More

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Human DDK rescues stalled forks and counteracts checkpoint inhibition at unfired origins to complete DNA replication.

Mol Cell 2021 02;81(3):426-441.e8

Molecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Eukaryotic genomes replicate via spatially and temporally regulated origin firing. Cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK) promote origin firing, whereas the S phase checkpoint limits firing to prevent nucleotide and RPA exhaustion. We used chemical genetics to interrogate human DDK with maximum precision, dissect its relationship with the S phase checkpoint, and identify DDK substrates. Read More

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February 2021

Single-Molecule Dynamics at a Bacterial Replication Fork after Nutritional Downshift or Chemically Induced Block in Replication.

mSphere 2021 01 27;6(1). Epub 2021 Jan 27.

SYNMIKRO, LOEWE Center for Synthetic Microbiology, Marburg, Germany

Replication forks must respond to changes in nutrient conditions, especially in bacterial cells. By investigating the single-molecule dynamics of replicative helicase DnaC, DNA primase DnaG, and lagging-strand polymerase DnaE in the model bacterium , we show that proteins react differently to stress conditions in response to transient replication blocks due to DNA damage, to inhibition of the replicative polymerase, or to downshift of serine availability. DnaG appears to be recruited to the forks by a diffusion and capture mechanism, becomes more statically associated after the arrest of polymerase, but binds less frequently after fork blocks due to DNA damage or to nutritional downshift. Read More

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January 2021

The Bloom syndrome complex senses RPA-coated single-stranded DNA to restart stalled replication forks.

Nat Commun 2021 01 26;12(1):585. Epub 2021 Jan 26.

MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.

The Bloom syndrome helicase BLM interacts with topoisomerase IIIα (TOP3A), RMI1 and RMI2 to form the BTR complex, which dissolves double Holliday junctions to produce non-crossover homologous recombination (HR) products. BLM also promotes DNA-end resection, restart of stalled replication forks, and processing of ultra-fine DNA bridges in mitosis. How these activities of the BTR complex are regulated in cells is still unclear. Read More

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January 2021

Programmed cell death-1 blockade in kidney carcinoma may induce eosinophilic granulomatosis with polyangiitis: a case report.

BMC Pulm Med 2021 Jan 6;21(1). Epub 2021 Jan 6.

Department of Respiratory Medicine, Fujieda Municipal General Hospital, 4-1-11 Surugadai, Fujieda City, Shizuoka Province, Japan.

Background: Immune checkpoint inhibitors have potential applications in treating various cancers but are associated with immune-related adverse events, such as inflammation, in a wide range of organs; however, allergic inflammation caused by these agents has not been extensively studied.

Case Presentation: A 65-year-old man was diagnosed with a kidney neuroendocrine carcinoma. Three months after kidney resection surgery, the tumor cells had metastasized to his liver and lymph nodes. Read More

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January 2021

DNA polymerase ι compensates for Fanconi anemia pathway deficiency by countering DNA replication stress.

Proc Natl Acad Sci U S A 2020 12 21;117(52):33436-33445. Epub 2020 Dec 21.

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;

Fanconi anemia (FA) is caused by defects in cellular responses to DNA crosslinking damage and replication stress. Given the constant occurrence of endogenous DNA damage and replication fork stress, it is unclear why complete deletion of FA genes does not have a major impact on cell proliferation and germ-line FA patients are able to progress through development well into their adulthood. To identify potential cellular mechanisms that compensate for the FA deficiency, we performed dropout screens in FA mutant cells with a whole genome guide RNA library. Read More

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December 2020

L-arabinose induces the formation of viable non-proliferating spheroplasts in .

Appl Environ Microbiol 2020 Dec 18. Epub 2020 Dec 18.

Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France

, the agent of the deadly human disease cholera, propagates as a curved rod-shaped bacterium in warm waters. It is sensitive to cold, but persists in cold waters under the form of viable but non-dividing coccoidal shaped cells. Additionally, is able to form non-proliferating spherical cells in response to cell wall damage. Read More

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December 2020

The ZATT-TOP2A-PICH Axis Drives Extensive Replication Fork Reversal to Promote Genome Stability.

Mol Cell 2021 01 8;81(1):198-211.e6. Epub 2020 Dec 8.

The MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address:

Replication fork reversal is a global response to replication stress in mammalian cells, but precisely how it occurs remains poorly understood. Here, we show that, upon replication stress, DNA topoisomerase IIalpha (TOP2A) is recruited to stalled forks in a manner dependent on the SNF2-family DNA translocases HLTF, ZRANB3, and SMARCAL1. This is accompanied by an increase in TOP2A SUMOylation mediated by the SUMO E3 ligase ZATT and followed by recruitment of a SUMO-targeted DNA translocase, PICH. Read More

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January 2021

Mechanisms of Theta Plasmid Replication in Enterobacteria and Implications for Adaptation to Its Host.

EcoSal Plus 2020 11;9(1)

Department of Microbiology and Environmental Toxicology, University of California at Santa Cruz, Santa Cruz, CA, 95064.

Plasmids are autonomously replicating sequences that help cells adapt to diverse stresses. Theta plasmids are the most frequent plasmid class in enterobacteria. They co-opt two host replication mechanisms: replication at , a DnaA-dependent pathway leading to replisome assembly (theta class A), and replication fork restart, a PriA-dependent pathway leading to primosome assembly through primer extension and D-loop formation (theta classes B, C, and D). Read More

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November 2020

Microcephalin 1/BRIT1-TRF2 interaction promotes telomere replication and repair, linking telomere dysfunction to primary microcephaly.

Nat Commun 2020 11 17;11(1):5861. Epub 2020 Nov 17.

Department of Laboratory Medicine, Yale University School of Medicine, 330 Cedar St., New Haven, CT, 06520, USA.

Telomeres protect chromosome ends from inappropriately activating the DNA damage and repair responses. Primary microcephaly is a key clinical feature of several human telomere disorder syndromes, but how microcephaly is linked to dysfunctional telomeres is not known. Here, we show that the microcephalin 1/BRCT-repeats inhibitor of hTERT (MCPH1/BRIT1) protein, mutated in primary microcephaly, specifically interacts with the TRFH domain of the telomere binding protein TRF2. Read More

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November 2020

Hypersensitive SSY1 mutations negatively influence transition to quiescence in yeast Saccharomyces cerevisiae.

Yeast 2021 01 1;38(1):102-116. Epub 2020 Dec 1.

Institute of Environmental Sciences, Faculty of Biology, Jagiellonian University, Krakow, Poland.

Most cells spend the majority of their life in the non-proliferating, quiescent state. Transition to this state is crucial for microorganisms to survive long starvation periods and restart divisions afterwards. Experimental evolution allowed us to identify several mutation in genes that are presumably important for such transition in yeast cells. Read More

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January 2021

Roles of OB-Fold Proteins in Replication Stress.

Front Cell Dev Biol 2020 11;8:574466. Epub 2020 Sep 11.

Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, United States.

Accurate DNA replication is essential for maintaining genome stability. However, this stability becomes vulnerable when replication fork progression is stalled or slowed - a condition known as replication stress. Prolonged fork stalling can cause DNA damage, leading to genome instabilities. Read More

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September 2020

RWR-algorithm-based dissection of microRNA-506-3p and microRNA-140-5p as radiosensitive biomarkers in colorectal cancer.

Aging (Albany NY) 2020 10 8;12(20):20512-20522. Epub 2020 Oct 8.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Radiotherapy resistance is one of the main causes for treatment failure in colorectal cancer (CRC), and it is associated with the deregulation of certain microRNAs. In this study, we constructed the microRNA-mRNA network consisting of 2275 microRNAs and 7045 target genes, collected the known microRNAs related to CRC-radiosensitivity (CRCR) (n=18) as the seed nodes, and applied the algorithm of random walk with restart (RWR) to the network to identify novel CRCR-related microRNAs (n=263). In functional analysis, 263 novel microRNAs shared a high proportion of the same biological processes and pathways with the known microRNAs. Read More

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October 2020

CK2 kinase-mediated PHF8 phosphorylation controls TopBP1 stability to regulate DNA replication.

Nucleic Acids Res 2020 11;48(19):10940-10952

Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.

ATR functions as a master regulator of the DNA-damage response. ATR activation requires the ATR activator, topoisomerase IIβ-binding protein 1 (TopBP1). However, the underlying mechanism of TopBP1 regulation and how its regulation affects DNA replication remain unknown. Read More

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November 2020

[Hurdles to HIV cure. Part 1 : the latent reservoirs].

Rev Med Liege 2020 Sep;75(9):573-577

Service des Maladies infectieuses et Médecine interne générale, CHU Liège, Belgique.

The human immunodeficiency virus (HIV), responsible for acquired immunodeficiency syndrome or AIDS, is a major public health problem. In Belgium, 2 to 3 new cases are diagnosed every day. Since the advent of combined antiretroviral treatments in 1996, the life expectancy and quality of life of infected patients have greatly improved. Read More

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September 2020

Mutational Analysis of Residues in PriA and PriC Affecting Their Ability To Interact with SSB in Escherichia coli K-12.

J Bacteriol 2020 11 4;202(23). Epub 2020 Nov 4.

Molecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, Massachusetts, USA

PriA and PriC recognize abandoned replication forks and direct reloading of the DnaB replicative helicase onto the lagging-strand template coated with single-stranded DNA-binding protein (SSB). Both PriA and PriC have been shown by biochemical and structural studies to physically interact with the C terminus of SSB. , these interactions trigger remodeling of the SSB on ssDNA. Read More

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November 2020