In Vivo measurement of unscheduled DNA synthesis and S-phase synthesis as an indicator of hepatocarcinogenesis in rodents

1987 ◽  
Vol 3 (2) ◽  
pp. 165-173 ◽  
Author(s):  
Jon C. Mirsalis
Keyword(s):  
Dna Synthesis ◽  
S Phase ◽  
Unscheduled Dna Synthesis ◽  
Phase Synthesis ◽  
In Vivo Measurement

Measurement of unscheduled DNA synthesis and S-phase synthesis in rodent hepatocytes following in vivo treatment: Testing of 24 compounds

1989 ◽  
Vol 14 (3) ◽  
pp. 155-164 ◽  
Author(s):  
Jon C. Mirsalis ◽  
C. Kim Tyson ◽  
Karen L. Steinmetz ◽  
Erica K. Loh ◽  
Carol M. Hamilton ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
S Phase ◽  
Unscheduled Dna Synthesis ◽  
Phase Synthesis ◽  
In Vivo Treatment

scholarly journals Lesions induced in DNA by ultraviolet light are repaired at the nuclear cage

1984 ◽  
Vol 70 (1) ◽  
pp. 189-196
Author(s):  
S.J. McCready ◽  
P.R. Cook
Keyword(s):  
Dna Synthesis ◽  
Ultraviolet Light ◽  
Hela Cells ◽  
Nuclear Matrix ◽  
Ultraviolet Irradiation ◽  
Mammalian Cells ◽  
Nuclear Dna ◽  
S Phase ◽  
Unscheduled Dna Synthesis ◽  
Phase Synthesis

In mammalian cells, S-phase DNA synthesis occurs at sites fixed to a sub-nuclear structure, the nuclear matrix or cage. This is an ordered network of non-histone proteins, which maintains its essential morphology even in the absence of DNA. We show here that unscheduled DNA synthesis following exposure of HeLa cells to ultraviolet light also takes place at this sub-structure. We also show that ultraviolet irradiation grossly reorganizes nuclear DNA, arresting S-phase synthesis at the cage and leaving the residual synthesis highly localized.

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.

scholarly journals The Schizosaccharomyces pombe rad11+ gene encodes the large subunit of replication protein A.

1997 ◽  
Vol 17 (5) ◽  
pp. 2381-2390 ◽  
Author(s):  
A E Parker ◽  
R K Clyne ◽  
A M Carr ◽  
T J Kelly
Keyword(s):  
Dna Repair ◽  
Dna Synthesis ◽  
Schizosaccharomyces Pombe ◽  
Excision Repair ◽  
Protein A ◽  
Simian Virus 40 ◽  
Replication Protein A ◽  
S Phase ◽  
Replication Protein

Replication protein A (RPA) is a heterotrimeric single-stranded DNA-binding protein present in all eukaryotes. In vitro studies have implicated RPA in simian virus 40 DNA synthesis and nucleotide excision repair, but little direct information is available about the in vivo roles of the protein. We report here the cloning of the largest subunit of RPA (rpa1+) from the fission yeast Schizosaccharomyces pombe. The rpa1+ gene is essential for viability and is expressed specifically at S phase of the cell cycle. Genetic analysis revealed that rpa1+ is the locus of the S. pombe radiation-sensitive mutation rad11. The rad11 allele exhibits pleiotropic effects consistent with an in vivo role for RPA in both DNA repair and DNA synthesis. The mutant is sensitive to both UV and ionizing radiation but is not defective in the DNA damage-dependent checkpoint, consistent with the hypothesis that RPA is part of the enzymatic machinery of DNA repair. When incubated in hydroxyurea, rad11 cells initially arrest with a 1C DNA content but then lose viability coincident with reentry into S phase, suggesting that DNA synthesis is aberrant under these conditions. A significant fraction of the mutant cells subsequently undergo inappropriate mitosis in the presence of hydroxyurea, indicating that RPA also plays a role in the checkpoint mechanism that monitors the completion of S phase. We propose that RPA is required to maintain the integrity of replication complexes when DNA replication is blocked. We further suggest that the rad11 mutation leads to the premature breakdown of such complexes, thereby preventing recovery from the hydroxyurea arrest and eliminating a signal recognized by the S-phase checkpoint mechanism.

Use of in Vivo/In Vitro Unscheduled Dna Synthesis for Identification of Organ-Specific Carcinogens

1987 ◽  
Vol 17 (3) ◽  
pp. 245-277 ◽  
Author(s):  
Chie Furihata ◽  
Taijiro Matsushima ◽  
Byron E. Butterworth
Keyword(s):  
Dna Synthesis ◽  
Unscheduled Dna Synthesis ◽  
Organ Specific
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