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        <datestamp>2026-09-28T17:53:23Z</datestamp>
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          <dc:title>&lt;p&gt;Cell cycle-associated variation of histones, kinases, and nucleotide metabolism-related proteins in the T. cruzi nuclear proteome.&lt;/p&gt;</dc:title>
          <dc:creator>Ana Paula Menezes (25132835)</dc:creator>
          <dc:creator>Camila Gachet-Castro (11579152)</dc:creator>
          <dc:creator>Suzanne McGill (11916067)</dc:creator>
          <dc:creator>Richard Burchmore (178746)</dc:creator>
          <dc:creator>Ariel Silber (25132838)</dc:creator>
          <dc:creator>Maria Carolina Elias (9906069)</dc:creator>
          <dc:creator>Júlia P. C. da Cunha (25132841)</dc:creator>
          <dc:subject>Biophysics</dc:subject>
          <dc:subject>Biochemistry</dc:subject>
          <dc:subject>Physical Sciences not elsewhere classified</dc:subject>
          <dc:subject>Medicine</dc:subject>
          <dc:subject>Cell Biology</dc:subject>
          <dc:subject>Genetics</dc:subject>
          <dc:subject>Molecular Biology</dc:subject>
          <dc:subject>Physiology</dc:subject>
          <dc:subject>Chemical Sciences not elsewhere classified</dc:subject>
          <dc:subject>Biological Sciences not elsewhere classified</dc:subject>
          <dc:subject>Developmental Biology</dc:subject>
          <dc:subject>Hematology</dc:subject>
          <dc:subject>Computational  Biology</dc:subject>
          <dc:subject>unique cellular features</dc:subject>
          <dc:subject>transition using hydroxyurea</dc:subject>
          <dc:subject>regulating fundamental processes</dc:subject>
          <dc:subject>pyruvate kinase activities</dc:subject>
          <dc:subject>maintaining genomic integrity</dc:subject>
          <dc:subject>hu ), followed</dc:subject>
          <dc:subject>cd ), represents</dc:subject>
          <dc:subject>specific expression patterns</dc:subject>
          <dc:subject>previously underappreciated role</dc:subject>
          <dc:subject>gene expression regulation</dc:subject>
          <dc:subject>canonical regulatory mechanisms</dc:subject>
          <dc:subject>&gt;, potentially influencing</dc:subject>
          <dc:subject>trypanosoma cruzi &lt;/</dc:subject>
          <dc:subject>purified nuclear fraction</dc:subject>
          <dc:subject>metabolic enzymes including</dc:subject>
          <dc:subject>gene expression</dc:subject>
          <dc:subject>metabolic enzymes</dc:subject>
          <dc:subject>cruzi &lt;/</dc:subject>
          <dc:subject>pivotal role</dc:subject>
          <dc:subject>variant histones</dc:subject>
          <dc:subject>valuable model</dc:subject>
          <dc:subject>temporal compartmentalization</dc:subject>
          <dc:subject>specialized organelles</dc:subject>
          <dc:subject>revealing distinct</dc:subject>
          <dc:subject>results suggest</dc:subject>
          <dc:subject>provide insights</dc:subject>
          <dc:subject>proteins involved</dc:subject>
          <dc:subject>proteins identified</dc:subject>
          <dc:subject>protein synthesis</dc:subject>
          <dc:subject>nucleoside metabolisms</dc:subject>
          <dc:subject>nuclear region</dc:subject>
          <dc:subject>nuclear proteome</dc:subject>
          <dc:subject>nuclear division</dc:subject>
          <dc:subject>microtubule dynamics</dc:subject>
          <dc:subject>increased levels</dc:subject>
          <dc:subject>immunofluorescence supported</dc:subject>
          <dc:subject>identified 2</dc:subject>
          <dc:subject>eukaryotic models</dc:subject>
          <dc:subject>etiological agent</dc:subject>
          <dc:subject>dna replication</dc:subject>
          <dc:subject>diverging eukaryotes</dc:subject>
          <dc:subject>citrate synthase</dc:subject>
          <dc:subject>chromosome condensation</dc:subject>
          <dc:description>&lt;p&gt;&lt;b&gt;(A)&lt;/b&gt; Relative abundance of canonical histones during G1/S, S, and G2/M phases. &lt;b&gt;(B)&lt;/b&gt; Relative abundance of histone variants during G1/S, S, and G2/M phases. &lt;b&gt;(C)&lt;/b&gt; Relative abundance profiles of selected kinases detected in the nuclear proteome, including metabolic kinases and signaling-associated kinases. &lt;b&gt;(D)&lt;/b&gt; Relative abundance of selected proteins associated with nucleotide metabolism across the cell cycle. Statistical significance was assessed by ANOVA (*p &lt; 0.05, **p &lt; 0.01). &lt;b&gt;(E)&lt;/b&gt; Schematic representation of nucleotide metabolism in T. cruzi, including pyrimidine de novo and salvage pathways and the purine salvage pathway. Enzymes are color-coded according to their detection and abundance variation across the cell cycle: orange, identified but not quantified; green, no significant variation; red, increased abundance in G1/S compared with S and G2/M; gray, decreased abundance in G2/M compared with S and G1/S; and white, not detected. Pyrimidine metabolism: carbamoyl-phosphate synthetase II (CPSII, EC:6.3.5.5), aspartate carbamoyltransferase (ATCase, EC:2.1.3.2), dihydroorotase (DHOase, EC:3.5.2.3), dihydroorotate dehydrogenase (DHODH, EC:1.3.98.1), orotate phosphoribosyltransferase (OPRT, EC:2.4.2.10), orotidine-5-phosphate decarboxylase (OMP, EC:4.1.1.23), uracil phosphoribosyltransferase (UPT, EC:2.4.2.9), UMP-CMP kinase 2 (UMPK, EC:2.7.4.22), cytidine triphosphate synthase (CTPS, EC:6.3.4.2), uridine-cytidine kinase (UCK, EC:2.7.1.48), nucleoside diphosphate kinase (NDK, EC:2.7.4.6), ribonucleoside-diphosphate reductase (RNR, EC:1.17.4.1), 5′-deoxynucleotidase (5′DN, EC:3.1.3.89), thymidylate kinase (TK, EC:2.7.4.9), and phosphoribosylpyrophosphate synthetase (PRPS, EC:2.7.6.1). Purine metabolism: inosine-adenosine-guanosine-nucleoside hydrolase (IGNH, EC:3.2.2.1), hypoxanthine-guanine phosphoribosyltransferase (HGPRT, EC:2.4.2.8), inosine-5′-monophosphate dehydrogenase (IMPDH/INMD, EC:1.1.1.205), guanylate kinase (GK, EC:2.7.4.8), adenosine kinase (AK, EC:2.7.1.20), and adenylate kinase (ADK, EC:2.7.4.3). Abbreviations: PRPP, phosphoribosyl pyrophosphate; AMP, adenosine monophosphate; ADP, adenosine diphosphate; ATP, adenosine triphosphate; dADP, deoxyadenosine diphosphate; dATP, deoxyadenosine triphosphate; IMP, inosine monophosphate; GMP, guanosine monophosphate; GDP, guanosine diphosphate; GTP, guanosine triphosphate; dGDP, deoxyguanosine diphosphate; dGTP, deoxyguanosine triphosphate; XMP, xanthosine monophosphate; UMP, uridine monophosphate; UDP, uridine diphosphate; UTP, uridine triphosphate; CMP, cytidine monophosphate; CDP, cytidine diphosphate; CTP, cytidine triphosphate; dCDP, deoxycytidine diphosphate; dCTP, deoxycytidine triphosphate; dTDP, deoxythymidine diphosphate; dTTP, deoxythymidine triphosphate.&lt;/p&gt;</dc:description>
          <dc:date>2026-09-28T17:59:59Z</dc:date>
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          <dc:identifier>10.1371/journal.pntd.0013299.g002</dc:identifier>
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