Crosstalk between signaling pathways and DNA damage response

Abstract

Living organisms have developed a complex signaling system to sense diverse growth signals and co-ordinate intracellular bioprocesses, so that they survive in various conditions. Since organisms are often exposed to environmental and genomic threats which cause DNA damages, DNA damage response (DDR) and repair systems are important for maintenance of genome stability and integrity. A line of evidences has demonstrated that there is tight crosstalk between growth signaling pathways and DDR systems. In this review, we give a brief overview of recent reports dissecting the interaction between signaling pathways and DDR at molecular level, which may further expand the knowledge of the signaling network and provide clues for disease therapy.

DNA Damage: From Threat to Treatment

“…Here, we provide a simple overview of these mechanisms. For a comprehensive description of the complex pathways involved, we refer the reader to extensive review articles previously published [ 11 , 12 , 13 ]. Interstrand crosslinks (ICLs), generated either by natural or synthetic compounds, are mostly resolved via the Fanconi Anemia (FA) pathway [ 14 ].…”

Mycoplasma hominis Causes DNA Damage and Cell Death in Primary Human Keratinocytes

“…Occasionally, the depletion of a specific nutrient, such as choline, can play an important role in inducing apoptosis in infected cells [ 50 ]. Arginine depletion may lead to the inhibition of the mTOR pathway, thus indirectly activating DNA damage pathways, such as ATM/ATR, which may also explain the cell cycle arrest and apoptosis in cells with a high microorganism load [ 51 ]. Furthermore, mycoplasma deaminases hydrolyse L-arginine into L-citrulline and NH 3 .…”

The Inducible Role of Ambient Particulate Matter in Cancer Progression via Oxidative Stress-Mediated Reactive Oxygen Species Pathways: A Recent Perception

“…Unfortunately, several studies have suggested that PM2.5 possibly decreases the DNA repair capacity [66,69]. Furthermore, recent investigations have found that DDR might be affected by crosstalk with a number of signaling pathways, such as PI3K/AKT, NF-kB and, so on [83]. As mentioned above, PM2.5-induced ROS production has been documented to activate these signaling pathways, further implicating its role in the interruption of DDR.…”

“…In fact, living organisms are always exposed to a variety of risk factors, both exogenous and endogenous, that might be harmful to genome stability and integrity, possibly leading to various types of DNA damage. Luckily, a complicated signaling network including DNA repair and cell cycle checkpoint pathways, also referred to as the DNA damage response (DDR), is activated in response to DNA damage in order to function as an "anti-cancer barrier" [83]. If compromised DNA is inappropriately restored by DDR, the genomic mutations and other irreversible damage will occur, subsequently leading to severe consequences such as malignant progression.…”