DNA Damage Response and Cell Cycle Regulation in Pluripotent Stem Cells

Pluripotent stem cells (PSCs) hold great promise in cell-based therapy because of their pluripotent property and the ability to proliferate indefinitely. Embryonic stem cells (ESCs) derived from inner cell mass (ICM) possess unique cell cycle control with shortened G1 phase. In addition, ESCs have h...

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Bibliographic Details
Published in:Genes 2021-09, Vol.12 (10), p.1548
Main Authors: Chen, Andy Chun Hang, Peng, Qian, Fong, Sze Wan, Lee, Kai Chuen, Yeung, William Shu Biu, Lee, Yin Lau
Format: Article
Language:English
Subjects:
Animals
c-Myc protein
Cell Cycle
Cell division
Cyclin-dependent kinases
Deoxyribonucleic acid
DNA
DNA Damage
DNA repair
Embryo cells
Fibroblasts
G1 phase
Gene expression
Gene regulation
Genomics
Homologous recombination
Humans
Kinases
KLF4 protein
Myc protein
Non-homologous end joining
Oct-4 protein
Oxidative stress
p53 Protein
Phosphorylation
Pluripotency
Pluripotent Stem Cells - metabolism
Pluripotent Stem Cells - physiology
Proteins
Review
SIRT1 protein
Stem cells
Transcription factors
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Summary:Pluripotent stem cells (PSCs) hold great promise in cell-based therapy because of their pluripotent property and the ability to proliferate indefinitely. Embryonic stem cells (ESCs) derived from inner cell mass (ICM) possess unique cell cycle control with shortened G1 phase. In addition, ESCs have high expression of homologous recombination (HR)-related proteins, which repair double-strand breaks (DSBs) through HR or the non-homologous end joining (NHEJ) pathway. On the other hand, the generation of induced pluripotent stem cells (iPSCs) by forced expression of transcription factors (Oct4, Sox2, Klf4, c-Myc) is accompanied by oxidative stress and DNA damage. The DNA repair mechanism of DSBs is therefore critical in determining the genomic stability and efficiency of iPSCs generation. Maintaining genomic stability in PSCs plays a pivotal role in the proliferation and pluripotency of PSCs. In terms of therapeutic application, genomic stability is the key to reducing the risks of cancer development due to abnormal cell replication. Over the years, we and other groups have identified important regulators of DNA damage response in PSCs, including , and . They function through transcription regulation of downstream targets ( , CDK1) that are involved in cell cycle regulations. Here, we review the fundamental links between the PSC-specific HR process and DNA damage response, with a focus on the roles of and on maintaining genomic integrity.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes12101548