Genome Maintenance in Mammalian Stem Cells

Abstract

Various stem cells in the body are tasked with maintaining tissue homeostasis throughout the life of an organism and thus must be resilient to intrinsic and extrinsic challenges such as infection and injury. Crucial to these challenges is genome maintenance because a high mutational load and persistent DNA lesions impact the production of essential gene products at proper levels and compromise optimal stem cell renewal and differentiation. Genome maintenance requires a robust and well-regulated DNA damage response suited to maintaining specific niches and tissues. In this review, we explore the similarities and differences between diverse stem cell types derived from (or preceding) all germ layers, including extraembryonic tissues. These cells utilize different strategies, including implementation of robust repair mechanisms, modulation of cell cycle checkpoints best suited to eliminating compromised cells, minimization of cell divisions, and differentiation in response to excessive damage. Expected final online publication date for the Annual Review of Genetics, Volume 56 is November 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

HR repair pathway plays a crucial role in maintaining neural stem cell fate under irradiation stress

“…During early development stages, stimulation of the metabolism, specific genetic background, and/or physical or chemical factors, can all cause the accumulation of damage to the genome. DNA damage repair defects can then lead to alterations of stem cell fate (Sang et al, 2022;Schimenti et al, 2022). Here, we show that a high (A, B, C, D') The MRN complex, consisting of mre11, Nbs, and Rad50, functions in the resection process when DSB occurs.…”

“…During early development stages, stimulation of the metabolism, specific genetic background, and/or physical or chemical factors, can all cause the accumulation of damage to the genome. DNA damage repair defects can then lead to alterations of stem cell fate ( Sang et al, 2022 ; Schimenti et al, 2022 ). Here, we show that a high dosage of X-ray IR induces DNA damage, in which the active DNA damage repair process is associated with nuclear Pros accumulation in NBs, resulting in premature differentiation and cell fate termination.…”

Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

“…If stress occurs during the cell cycle, this effect may be even stronger because the cell cycle genes are also mostly of UC origin. In addition, stress increases the mutation rate due to both direct damage by stressful conditions (e.g., by reactive oxygen species) and ancient error-prone DNA repair, especially during the cell cycle when the genome occurs in a most vulnerable state, called ‘proliferation stress’ [ 66 , 67 , 68 ]. The relationship between the tissue proliferation activity and the probability of cancer was shown [ 69 ].…”