Effects of 8-halo-7-deaza-2′-deoxyguanosine triphosphate on DNA synthesis by DNA polymerases and cell proliferation

2016 ◽  
Vol 24 (16) ◽  
pp. 3856-3861 ◽  
Author(s):  
Yizhen Yin ◽  
Shigeki Sasaki ◽  
Yosuke Taniguchi
Keyword(s):  
Cell Proliferation ◽  
Dna Synthesis ◽  
Dna Polymerases ◽  
Deoxyguanosine Triphosphate

Effective Utilization ofN2-Ethyl-2‘-deoxyguanosine Triphosphate during DNA Synthesis Catalyzed by Mammalian Replicative DNA Polymerases†

Biochemistry ◽  
1999 ◽  
Vol 38 (3) ◽  
pp. 929-935 ◽  
Author(s):  
Tomonari Matsuda ◽  
Isamu Terashima ◽  
Yoshihiro Matsumoto ◽  
Hisatoshi Yabushita ◽  
Saburo Matsui ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Dna Polymerases ◽  
Effective Utilization ◽  
Deoxyguanosine Triphosphate

Genotoxicity and Cell Proliferative Activity of 3-Chloro-4-(Dichloromethyl)-5-Hydroxy-2(5H)-Furanone [MX] in Rat Glandular Stomach

1992 ◽  
Vol 25 (11) ◽  
pp. 341-345 ◽  
Author(s):  
C. Furihata ◽  
M. Yamashita ◽  
N. Kinae ◽  
T. Matsushima
Keyword(s):  
Cell Proliferation ◽  
Body Weight ◽  
Dna Synthesis ◽  
Ornithine Decarboxylase ◽  
Tap Water ◽  
Fold Increase ◽  
Single Strand ◽  
Glandular Stomach ◽  
Decarboxylase Activity ◽  
Pyloric Mucosa

MX is a strong direct acting mutagen on Salmonella typhimurium TA100 and is present in chlorinated tap water which contains organic compounds. MX was administered orally to 7-week-old male F344 rats, and its geno-toxicity in the pyloric mucosa of stomach was examined by analysis of DNA single strand scissions by the alkaline elution method. The effect of MX on cell proliferation was examined by assays of the inductions of replicative DNA synthesis and ornithine decarboxylase. MX at closes of 20-48 mg/kg body weight induced DNA single strand scissions dose-dependently (p<0.02) in the pyloric mucosa of the stomach 2 h after its administration. Moreover at doses of 10-60 mg/kg body weight, it induced up to 21-fold increase in replicative DNA synthesis (p<0.01) 16 h after its administration. At doses of 10-60 mg/kg body weight, it induced up to 100-fold increase in ornithine decarboxylase activity with a maximum 16 h after its administration. These results suggest that MX is genotoxic and induces cell proliferation in the glandular stomach of rats.

scholarly journals CRISPR-Associated Primase-Polymerases are implicated in prokaryotic CRISPR-Cas adaptation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Katerina Zabrady ◽  
Matej Zabrady ◽  
Peter Kolesar ◽  
Arthur W. H. Li ◽  
Aidan J. Doherty
Keyword(s):  
Dna Repair ◽  
Dna Synthesis ◽  
Genome Stability ◽  
Dna Polymerases ◽  
Acquired Immunity ◽  
Strand Displacement ◽  
Genetic Studies ◽  
Type Iiia ◽  
Maintain Genome Stability ◽  
Cas Proteins

AbstractCRISPR-Cas pathways provide prokaryotes with acquired “immunity” against foreign genetic elements, including phages and plasmids. Although many of the proteins associated with CRISPR-Cas mechanisms are characterized, some requisite enzymes remain elusive. Genetic studies have implicated host DNA polymerases in some CRISPR-Cas systems but CRISPR-specific replicases have not yet been discovered. We have identified and characterised a family of CRISPR-Associated Primase-Polymerases (CAPPs) in a range of prokaryotes that are operonically associated with Cas1 and Cas2. CAPPs belong to the Primase-Polymerase (Prim-Pol) superfamily of replicases that operate in various DNA repair and replication pathways that maintain genome stability. Here, we characterise the DNA synthesis activities of bacterial CAPP homologues from Type IIIA and IIIB CRISPR-Cas systems and establish that they possess a range of replicase activities including DNA priming, polymerisation and strand-displacement. We demonstrate that CAPPs operonically-associated partners, Cas1 and Cas2, form a complex that possesses spacer integration activity. We show that CAPPs physically associate with the Cas proteins to form bespoke CRISPR-Cas complexes. Finally, we propose how CAPPs activities, in conjunction with their partners, may function to undertake key roles in CRISPR-Cas adaptation.

scholarly journals A MYBL2 complex for RRM2 transactivation and the synthetic effect of MYBL2 knockdown with WEE1 inhibition against colorectal cancer

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Qian Liu ◽  
Lijuan Guo ◽  
Hongyan Qi ◽  
Meng Lou ◽  
Rui Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Dna Synthesis ◽  
Ectopic Expression ◽  
Building Blocks ◽  
Small Subunit ◽  
S Phase ◽  
Clinical Samples ◽  
Dependent Manner

AbstractRibonucleotide reductase (RR) is a unique enzyme for the reduction of NDPs to dNDPs, the building blocks for DNA synthesis and thus essential for cell proliferation. Pan-cancer profiling studies showed that RRM2, the small subunit M2 of RR, is abnormally overexpressed in multiple types of cancers; however, the underlying regulatory mechanisms in cancers are still unclear. In this study, through searching in cancer-omics databases and immunohistochemistry validation with clinical samples, we showed that the expression of MYBL2, a key oncogenic transcriptional factor, was significantly upregulated correlatively with RRM2 in colorectal cancer (CRC). Ectopic expression and knockdown experiments indicated that MYBL2 was essential for CRC cell proliferation, DNA synthesis, and cell cycle progression in an RRM2-dependent manner. Mechanistically, MYBL2 directly bound to the promoter of RRM2 gene and promoted its transcription during S-phase together with TAF15 and MuvB components. Notably, knockdown of MYBL2 sensitized CRC cells to treatment with MK-1775, a clinical trial drug for inhibition of WEE1, which is involved in a degradation pathway of RRM2. Finally, mouse xenograft experiments showed that the combined suppression of MYBL2 and WEE1 synergistically inhibited CRC growth with a low systemic toxicity in vivo. Therefore, we propose a new regulatory mechanism for RRM2 transcription for CRC proliferation, in which MYBL2 functions by constituting a dynamic S-phase transcription complex following the G1/early S-phase E2Fs complex. Doubly targeting the transcription and degradation machines of RRM2 could produce a synthetic inhibitory effect on RRM2 level with a novel potential for CRC treatment.

Selective inhibition of cell proliferation and DNA synthesis by the polysulphated carbohydrate ι-carrageenan

1995 ◽  
Vol 36 (4) ◽  
pp. 325-334 ◽  
Author(s):  
Richard Hoffman ◽  
Walter Woodrow Burns ◽  
Dietrich H. Paper
Keyword(s):  
Cell Proliferation ◽  
Dna Synthesis ◽  
Selective Inhibition

scholarly journals Induction of pancreatic acinar cell proliferation by thyroid hormone

2005 ◽  
Vol 185 (3) ◽  
pp. 393-399 ◽  
Author(s):  
G M Ledda-Columbano ◽  
A Perra ◽  
M Pibiri ◽  
F Molotzu ◽  
A Columbano
Keyword(s):  
Cell Proliferation ◽  
Thyroid Hormone ◽  
Dna Synthesis ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Labeling Index ◽  
Metabolic Effects ◽  
Brdu Incorporation ◽  
Pancreatic Cell

Thyroid hormone is known to elicit diverse cellular and metabolic effects in various organs, including mitogenesis in the rat liver. In the present study, experiments were carried out to determine whether thyroid hormone is able to stimulate cell proliferation in another quiescent organ such as the pancreas. 3,5,3′-l-tri-iodothyronine (T3) added to the diet at a concentration of 4 mg/kg caused a striking increase in nuclear bromodeoxyuridine (BrdU) incorporation of rat acinar cells 7 days after treatment (the labeling index was 46.7% in T3-treated rats vs 7.1% in controls). BrdU incorporation was limited to the acinar cells, with duct cells and islet cells being essentially negative. The increase in DNA synthesis was accompanied by the presence of several mitotic figures. Histological examination of the pancreas did not exhibit any sign of T3-induced toxicity. Determination of the apoptotic index, measurement of the serum levels of α-amylase and lipase, and glycemia determination did not show any increase over control values, suggesting that the enhanced proliferation of acinar cells was a direct effect induced by T3 and not a regenerative response consequent to acinar or β-cell injury. Additional experiments showed that DNA synthesis was induced as early as 2 days after T3 treatment (the labeling index was 9.4 vs 1.9% in controls) and was associated with increased protein levels of cyclin D1, cyclin A and proliferating cell nuclear antigen, with no substantial differences in the expression of the cyclin-dependent kinase inhibitor p27. The mitogenic effect of T3 on the pancreas was not limited to the rat, since extensive acinar cell proliferation was also observed in the pancreas of mice treated with T3 for 1 week (the labeling index was 28% in T3-treated mice vs 1.8% in controls). Treatment with three other ligands of nuclear receptors, ciprofibrate, all-trans retinoic acid and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, induced little or no pancreatic cell proliferation. These results demonstrated that T3 is a powerful inducer of cell proliferation in the pancreas and suggested that pancreatic acinar cell proliferation by selected agents may have potential for therapeutic use.

Sign in / Sign up

Export Citation Format

Share Document