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

Failure of the peroxisome proliferator WY-14,643 to induce unscheduled DNA synthesis in rat hepatocytes following in vivo treatment

1988 ◽  
Vol 9 (7) ◽  
pp. 1179-1184 ◽  
Author(s):  
Russell C. Cattley ◽  
Tracey Smith-Oliver ◽  
Byron E. Butterworth ◽  
James A. Popp
Keyword(s):  
Dna Synthesis ◽  
Rat Hepatocytes ◽  
Peroxisome Proliferator ◽  
Unscheduled Dna Synthesis ◽  
In Vivo Treatment

Induction of hepatic cell proliferation and unscheduled DNA synthesis in mouse hepatocytes following in vivo treatment

1985 ◽  
Vol 6 (10) ◽  
pp. 1521-1524 ◽  
Author(s):  
Jon C. Mirsalis ◽  
C. Kimerly Tyson ◽  
Erica N. Loh ◽  
Karen L. Steinmetz ◽  
James P. Bakke ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dna Synthesis ◽  
Hepatic Cell ◽  
Unscheduled Dna Synthesis ◽  
Mouse Hepatocytes ◽  
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.

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