Maize Thymidine Kinase Activity Is Present throughout Plant Development and Its Heterologous Expression Confers Tolerance to an Organellar DNA-Damaging Agent

Manuela Nájera-Martínez; José Antonio Pedroza-García; Luis Jiro Suzuri-Hernández; Christelle Mazubert; Jeannine Drouin-Wahbi; Jorge Vázquez-Ramos; Cécile Raynaud; Javier Plasencia

doi:10.3390/plants9080930

Maize Thymidine Kinase Activity Is Present throughout Plant Development and Its Heterologous Expression Confers Tolerance to an Organellar DNA-Damaging Agent

Plants ◽

10.3390/plants9080930 ◽

2020 ◽

Vol 9 (8) ◽

pp. 930

Author(s):

Manuela Nájera-Martínez ◽

José Antonio Pedroza-García ◽

Luis Jiro Suzuri-Hernández ◽

Christelle Mazubert ◽

Jeannine Drouin-Wahbi ◽

...

Keyword(s):

Thymidine Kinase ◽

Developmental Stages ◽

Genotoxic Stress ◽

Genome Replication ◽

Organellar Dna ◽

Pyrimidine Salvage ◽

Model Plant Arabidopsis Thaliana ◽

Genome Copy Number ◽

Albino Phenotype

Thymidine kinase 1 (TK1) phosphorylates thymidine nucleosides to generate thymidine monophosphate. This reaction belongs to the pyrimidine salvage route that is phylogenetically conserved. In the model plant Arabidopsis thaliana, TK activity contributes to maintain nuclear and organellar genome integrity by providing deoxythymidine-triphosphate (dTTP) for DNA synthesis. Arabidopsis has two TK1 genes (TK1a and TK1b) and double mutants show an albino phenotype and develop poorly. In contrast, maize (Zea mays L.) has a single TK1 (ZmTK1) gene and mutant plants are albino and display reduced genome copy number in chloroplasts. We studied the role of ZmTK1 during development and genotoxic stress response by assessing its activity at different developmental stages and by complementing Arabidopsis tk1 mutants. We found that ZmTK1 transcripts and activity are present during germination and throughout maize development. We show that ZmTK1 translocation to chloroplasts depends on a 72-amino-acid N-signal and its plastid localization is consistent with its ability to complement Arabidopsis tk1b mutants which are hypersensitive to ciprofloxacin (CIP), a genotoxic agent to organellar DNA. Also, ZmTK1 partly complemented the Arabidopsis double mutant plants during development. Our results contribute to the understanding of TK1 function in monocot species as an organellar enzyme for genome replication and repair.

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Plant Organelle Genome Replication

Plants ◽

10.3390/plants8100358 ◽

2019 ◽

Vol 8 (10) ◽

pp. 358 ◽

Cited By ~ 2

Author(s):

Stewart A. Morley ◽

Niaz Ahmad ◽

Brent L. Nielsen

Keyword(s):

Copy Number ◽

Plant Mitochondria ◽

Plant Tissues ◽

Genome Replication ◽

Genome Copy ◽

Atp Production ◽

Organelle Dna ◽

Organellar Dna ◽

Multiple Processes ◽

Genome Copy Number

Mitochondria and chloroplasts perform essential functions in respiration, ATP production, and photosynthesis, and both organelles contain genomes that encode only some of the proteins that are required for these functions. The proteins and mechanisms for organelle DNA replication are very similar to bacterial or phage systems. The minimal replisome may consist of DNA polymerase, a primase/helicase, and a single-stranded DNA binding protein (SSB), similar to that found in bacteriophage T7. In Arabidopsis, there are two genes for organellar DNA polymerases and multiple potential genes for SSB, but there is only one known primase/helicase protein to date. Genome copy number varies widely between type and age of plant tissues. Replication mechanisms are only poorly understood at present, and may involve multiple processes, including recombination-dependent replication (RDR) in plant mitochondria and perhaps also in chloroplasts. There are still important questions remaining as to how the genomes are maintained in new organelles, and how genome copy number is determined. This review summarizes our current understanding of these processes.

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Contribution of Cytidine Deaminase to Thymidylate Biosynthesis in Trypanosoma brucei: Intracellular Localization and Properties of the Enzyme

mSphere ◽

10.1128/msphere.00374-19 ◽

2019 ◽

Vol 4 (4) ◽

Cited By ~ 1

Author(s):

Ana Moro-Bulnes ◽

Víctor M. Castillo-Acosta ◽

Maria Valente ◽

Juana Carrero-Lérida ◽

Guiomar Pérez-Moreno ◽

...

Keyword(s):

Thymidine Kinase ◽

Trypanosoma Brucei ◽

De Novo ◽

Cytidine Deaminase ◽

Intracellular Localization ◽

Pyrimidine Metabolism ◽

Content Type ◽

Pyrimidine Salvage ◽

Hydrolytic Deamination

ABSTRACT Cytidine deaminase (CDA) is a pyrimidine salvage enzyme that catalyzes cytidine and deoxycytidine hydrolytic deamination to yield uridine and deoxyuridine. Here we report the biochemical characterization of Trypanosoma brucei CDA as an enzyme within the tetrameric class of the CDA family that efficiently deaminates cytidine, deoxycytidine, and the nucleoside analogue 5-methyl-2′-deoxycytidine. In line with previous studies, we show that RNA interference (RNAi)-mediated CDA depletion impairs T. brucei proliferation when grown in pyrimidine-deficient medium, while supplementation with thymidine or deoxyuridine restores growth, further underscoring the role of this enzyme in providing deoxyuridine for dUMP formation via thymidine kinase, the substrate required for de novo thymidylate biosynthesis. This observation contrasts with the existence in T. brucei of a dimeric deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase), an essential enzyme that can produce dUMP via the hydrolysis of dUTP/dUDP. Thus, T. brucei dUTPase-null mutants are thymidine auxotrophs, suggesting that dUTPase might have a role in providing dUMP for thymidylate biosynthesis. We show that overexpression of human dCMP deaminase (DCTD), an enzyme that provides directly dUMP through dCMP deamination, does not reverse the lethal phenotype of dUTPase knockout cells, which further supports the notion that in T. brucei, CDA is uniquely involved in providing dUMP, while the main role of dUTPase would be the withdrawal of the excess of dUTP to avoid its incorporation into DNA. Furthermore, we report the mitochondrial localization of CDA, highlighting the importance of this organelle in pyrimidine metabolism. IMPORTANCE Cytidine deaminases (CDAs) catalyze the hydrolytic deamination of cytidine and deoxycytidine in the pyrimidine salvage pathway. In kinetoplastids, pyrimidine metabolism has been extensively studied as a source of potential drug targets, given the fact that many of the enzymes of the pathway are essential. Thymidylate (dTMP) synthesis in Trypanosoma brucei exhibits unique characteristics. Thus, it has been suggested that the production of dUMP, the substrate for dTMP formation, is solely dependent on cytidine deaminase and thymidine kinase. Here we characterize recombinant T. brucei CDA (TbCDA) and present evidence that indeed the alternative route for dUMP formation via deoxyuridine 5′-triphosphate nucleotidohydrolase does not have a prominent role in de novo dTMP formation. Furthermore, we provide a scheme for the compartmentalization of dTMP biosynthesis, taking into account the observation that CDA is located in the mitochondrion, together with available information on the intracellular localization of other enzymes involved in the dTTP biosynthetic pathway.

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Crayfish hemocytes develop along the granular cell lineage

Scientific Reports ◽

10.1038/s41598-021-92473-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fang Li ◽

Zaichao Zheng ◽

Hongyu Li ◽

Rongrong Fu ◽

Limei Xu ◽

...

Keyword(s):

Developmental Stages ◽

Cell Lineage ◽

Granular Cell ◽

Marker Genes ◽

Hematopoietic Tissue ◽

Differentiated Cells ◽

Stage Of Development ◽

Almost All ◽

Relationship Of

AbstractDespite the central role of hemocytes in crustacean immunity, the process of hemocyte differentiation and maturation remains unclear. In some decapods, it has been proposed that the two main types of hemocytes, granular cells (GCs) and semigranular cells (SGCs), differentiate along separate lineages. However, our current findings challenge this model. By tracking newly produced hemocytes and transplanted cells, we demonstrate that almost all the circulating hemocytes of crayfish belong to the GC lineage. SGCs and GCs may represent hemocytes of different developmental stages rather than two types of fully differentiated cells. Hemocyte precursors produced by progenitor cells differentiate in the hematopoietic tissue (HPT) for 3 ~ 4 days. Immature hemocytes are released from HPT in the form of SGCs and take 1 ~ 3 months to mature in the circulation. GCs represent the terminal stage of development. They can survive for as long as 2 months. The changes in the expression pattern of marker genes during GC differentiation support our conclusions. Further analysis of hemocyte phagocytosis indicates the existence of functionally different subpopulations. These findings may reshape our understanding of crustacean hematopoiesis and may lead to reconsideration of the roles and relationship of circulating hemocytes.

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Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer

ESMO Open ◽

10.1016/j.esmoop.2021.100076 ◽

2021 ◽

Vol 6 (2) ◽

pp. 100076

Author(s):

A. Matikas ◽

K. Wang ◽

E. Lagoudaki ◽

B. Acs ◽

I. Zerdes ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Thymidine Kinase ◽

Early Breast Cancer ◽

Prognostic Role ◽

Thymidine Kinase 1 ◽

Serum Thymidine Kinase 1

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Epigenetic transgenerational inheritance, Gametogenesis and Germline Development

Biology of Reproduction ◽

10.1093/biolre/ioab085 ◽

2021 ◽

Author(s):

Millissia Ben Maamar ◽

Eric E Nilsson ◽

Michael K Skinner

Keyword(s):

Developmental Biology ◽

Environmental Factors ◽

Biological System ◽

Developmental Stages ◽

Primordial Germ Cell ◽

Cell Types ◽

Transgenerational Inheritance ◽

Germline Development ◽

Current Review

Abstract One of the most important developing cell types in any biological system is the gamete (sperm and egg). The transmission of phenotypes and optimally adapted physiology to subsequent generations is in large part controlled by gametogenesis. In contrast to genetics, the environment actively regulates epigenetics to impact the physiology and phenotype of cellular and biological systems. The integration of epigenetics and genetics is critical for all developmental biology systems at the cellular and organism level. The current review is focused on the role of epigenetics during gametogenesis for both the spermatogenesis system in the male and oogenesis system in the female. The developmental stages from the initial primordial germ cell through gametogenesis to the mature sperm and egg are presented. How environmental factors can influence the epigenetics of gametogenesis to impact the epigenetic transgenerational inheritance of phenotypic and physiological change in subsequent generations is reviewed.

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The role of thymidine kinase in cancer diseases

Expert Opinion on Medical Diagnostics ◽

10.1517/17530059.2.2.129 ◽

2008 ◽

Vol 2 (2) ◽

pp. 129-141 ◽

Cited By ~ 39

Author(s):

Ondrej Topolcan ◽

Lubos Holubec

Keyword(s):

Thymidine Kinase ◽

Cancer Diseases

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Exploring the multiple roles of guardian of the genome: P53

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-020-00089-x ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Wasim Feroz ◽

Arwah Mohammad Ali Sheikh

Keyword(s):

Cell Cycle ◽

Dna Repair ◽

Crucial Role ◽

Cellular Response ◽

Genotoxic Stress ◽

Specific Response ◽

Main Body ◽

Repair System ◽

Tumour Suppression

Abstract Background Cells have evolved balanced mechanisms to protect themselves by initiating a specific response to a variety of stress. The TP53 gene, encoding P53 protein, is one of the many widely studied genes in human cells owing to its multifaceted functions and complex dynamics. The tumour-suppressing activity of P53 plays a principal role in the cellular response to stress. The majority of the human cancer cells exhibit the inactivation of the P53 pathway. In this review, we discuss the recent advancements in P53 research with particular focus on the role of P53 in DNA damage responses, apoptosis, autophagy, and cellular metabolism. We also discussed important P53-reactivation strategies that can play a crucial role in cancer therapy and the role of P53 in various diseases. Main body We used electronic databases like PubMed and Google Scholar for literature search. In response to a variety of cellular stress such as genotoxic stress, ischemic stress, oncogenic expression, P53 acts as a sensor, and suppresses tumour development by promoting cell death or permanent inhibition of cell proliferation. It controls several genes that play a role in the arrest of the cell cycle, cellular senescence, DNA repair system, and apoptosis. P53 plays a crucial role in supporting DNA repair by arresting the cell cycle to purchase time for the repair system to restore genome stability. Apoptosis is essential for maintaining tissue homeostasis and tumour suppression. P53 can induce apoptosis in a genetically unstable cell by interacting with many pro-apoptotic and anti-apoptotic factors. Furthermore, P53 can activate autophagy, which also plays a role in tumour suppression. P53 also regulates many metabolic pathways of glucose, lipid, and amino acid metabolism. Thus under mild metabolic stress, P53 contributes to the cell’s ability to adapt to and survive the stress. Conclusion These multiple levels of regulation enable P53 to perform diversified roles in many cell responses. Understanding the complete function of P53 is still a work in progress because of the inherent complexity involved in between P53 and its target proteins. Further research is required to unravel the mystery of this Guardian of the genome “TP53”.

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Improving Juvenile Justice for Females: A Statewide Assessment in California

Crime & Delinquency ◽

10.1177/001112802237128 ◽

2002 ◽

Vol 48 (4) ◽

pp. 526-552 ◽

Cited By ~ 35

Author(s):

Barbara Bloom ◽

Barbara Owen ◽

Elizabeth Piper Deschenes ◽

Jill Rosenbaum

Keyword(s):

Developmental Stages ◽

State Agencies ◽

Specific Policy ◽

Statewide Assessment ◽

Female Adolescence ◽

Staffing And Training ◽

Substance Abuse Education ◽

Gender Specific ◽

And Training

This article reports findings from a survey of officials from various California state agencies and a series of interviews and focus groups with female youth and professionals serving this population. The study examined types of services provided, program barriers, and facilitation of change. The findings were used to make gender-specific policy and program recommendations. The authors found that meeting the needs of girls and young women requires specialized staffing and training, particularly in terms of relationship and communication skills, gender differences in delinquency, substance abuse education, the role of abuse, developmental stages of female adolescence, and available programs and appropriate placements and limitations. Effective programming for girls and women should be shaped by and tailored to their real-world situations and problems. In order to do this, a theoretical approach to treatment that is gender-sensitive and that addresses the realities of girls' lives must be developed.

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Characterization of the Drosophila protein arginine methyltransferases DART1 and DART4

Biochemical Journal ◽

10.1042/bj20031176 ◽

2004 ◽

Vol 379 (2) ◽

pp. 283-289 ◽

Cited By ~ 47

Author(s):

Marie-Chloé BOULANGER ◽

Tina Branscombe MIRANDA ◽

Steven CLARKE ◽

Marco di FRUSCIO ◽

Beat SUTER ◽

...

Keyword(s):

Rna Binding ◽

Developmental Stages ◽

Rna Binding Proteins ◽

Genetic System ◽

Arginine Methylation ◽

Type I ◽

Protein Arginine Methyltransferases ◽

Arginine Residues ◽

Drosophila Protein

The role of arginine methylation in Drosophila melanogaster is unknown. We identified a family of nine PRMTs (protein arginine methyltransferases) by sequence homology with mammalian arginine methyltransferases, which we have named DART1 to DART9 (Drosophilaarginine methyltransferases 1–9). In keeping with the mammalian PRMT nomenclature, DART1, DART4, DART5 and DART7 are the putative homologues of PRMT1, PRMT4, PRMT5 and PRMT7. Other DART family members have a closer resemblance to PRMT1, but do not have identifiable homologues. All nine genes are expressed in Drosophila at various developmental stages. DART1 and DART4 have arginine methyltransferase activity towards substrates, including histones and RNA-binding proteins. Amino acid analysis of the methylated arginine residues confirmed that both DART1 and DART4 catalyse the formation of asymmetrical dimethylated arginine residues and they are type I arginine methyltransferases. The presence of PRMTs in D. melanogaster suggest that flies are a suitable genetic system to study arginine methylation.

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