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β-nicotinamide mononucleotide (NMN) is the precursor of coenzyme I nicotinamide adenine dinucleotide (NAD+), which plays a crucial role in complicated cellular processes, including DNA damage sig- naling pathways, redox reaction, and metabolic reaction. Supplementation of NMN to increase concentration of intracellular NAD and enhance the capacity of DNA damage repair has become a spot of research worldwide. This review provided an overview of latest research advancements in NMN, focusing on its potential in dela- ying aging, treating diseases, maintaining genomic stability, and cellular homeostasis. The mechanism of NMN's enhancement of host DNA damage repair ability was analyzed, and the potential risks of supplemen- ting NMN were discussed to provide reference for subsequent NMN-related scientific research. [ABSTRACT FROM AUTHOR]

Purpose: Cervical cancer is the fourth most common cause of cancer-associated mortality in women worldwide. Previous studies have reported that microRNAs (miRNAs) are involved in multiple biological aspects of cancer progression by regulating gene expression. Here, we investigated the role of microRNA-708 (miR-708) in cervical cancer. Methods: The expression levels of miR-708 in cervical cancer tissues and paired-normal cervical tissues were tested by quantitative polymerase chain reaction (qPCR). The interaction between miR-708 and Timeless was identified by bioinformatics method, dual-luciferase reporter assay, and Western blotting. The effects of over-expression of miR-708 on cell proliferation and cisplatin sensitivity were determined by Cell Counting Kit-8 (CCK-8) and colony formation assay. Cell cycle and apoptosis were analyzed by flow cytometry. DNA damage induced by over-expression of miR-708 was determined by comet assay. Expression levels of the genes involved in repair of DNA damage were analyzed by Western blotting. Results: MiR-708 was down-regulated in cervical cancer tissues compared with paired-normal cervical tissues. By bioinformatics method, Western blotting, and dual-luciferase reporter assay, we found that Timeless was a direct target of miR-708. Furthermore, miR-708 suppressed cellular viability, colony formation, promoted apoptosis, and induced DNA damage levels. MiR-708 also enhanced chemosensitivity of cervical cancer cells to cDDP via impairing the ATR/CHK1 signaling pathway. Conclusion: We conclude that miR-708 suppresses cell proliferation, facilitates cisplatin efficacy, and impairs DNA repair pathway in cervical cancer cells. These results demonstrate that miR-708 might be a candidate therapeutic target for future cervical cancer therapy. [ABSTRACT FROM AUTHOR]

DNA is an entity shielded by mechanisms that maintain genomic stability and are essential for living cells; however, DNA is constantly subject to assaults from the environment throughout the cellular life span, making the genome susceptible to mutation and irreparable damage. Cells are prepared to mend such events through cell death as an extrema ratio to solve those threats from a multicellular perspective. However, in cells under various stress conditions, checkpoint mechanisms are activated to allow cells to have enough time to repair the damaged DNA. In yeast, entry into the cell cycle when damage is not completely repaired represents an adaptive mechanism to cope with stressful conditions. In multicellular organisms, entry into cell cycle with damaged DNA is strictly forbidden. However, in cancer development, individual cells undergo checkpoint adaptation, in which most cells die, but some survive acquiring advantageous mutations and selfishly evolve a conflictual behavior. In this review, we focus on how, in cancer development, cells rely on checkpoint adaptation to escape DNA stress and ultimately to cell death.

Checkpoint adaptation was originally described in Saccharomyces Cerevisiae as the ability to divide following a sustained checkpoint arrest in the presence of unrepairable DNA breaks. A process of checkpoint adaptation was also reported in Xenopus in response to the replication inhibitor aphidicolin. Recently, we showed that checkpoint adaptation also occurs in human cells. Although cells undergoing checkpoint adaptation will frequently die in subsequent cell cycles owing to excessive DNA damage, some of the cells may be able to survive and proliferate with damaged DNA. Thus, checkpoint adaptation in human cells may potentially promote genomic instability and lead to cancer. Here, I discuss the current evidence for checkpoint adaptation in human cells and possible mechanisms and implications of this phenomenon.Oncogene (2007) 26, 5833–5839. doi:10.1038/sj.onc.1210402; published online 26 March 2007 [ABSTRACT FROM AUTHOR]

DNA is an entity shielded by mechanisms that maintain genomic stability and are essential for living cells; however, DNA is constantly subject to assaults from the environment throughout the cellular life span, making the genome susceptible to mutation and irreparable damage. Cells are prepared to mend such events through cell death as an extrema ratio to solve those threats from a multicellular perspective. However, in cells under various stress conditions, checkpoint mechanisms are activated to allow cells to have enough time to repair the damaged DNA. In yeast, entry into the cell cycle when damage is not completely repaired represents an adaptive mechanism to cope with stressful conditions. In multicellular organisms, entry into cell cycle with damaged DNA is strictly forbidden. However, in cancer development, individual cells undergo checkpoint adaptation, in which most cells die, but some survive acquiring advantageous mutations and selfishly evolve a conflictual behavior. In this review, we focus on how, in cancer development, cells rely on checkpoint adaptation to escape DNA stress and ultimately to cell death. [ABSTRACT FROM AUTHOR]