ArticleThe Journal of biological chemistry2014
Human pluripotent stem cells have a novel mismatch repair-dependent damage response.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Human MutLα activates methylpurine DNA glycosylase to induce alkylation damage cytotoxicity.bioRxiv : the preprint server for biology · 2025Article
- Precise correction of G6PD Viangchan mutation in iPSCs by prime editing strategy.Scientific reports · 2025Article
- Prime Editing in Dividing and Quiescent Cells.International journal of molecular sciences · 2025Review
- Comprehensive whole-genome sequencing reveals origins of mutational signatures associated with aging, mismatch repair deficiency and temozolomide chemotherapy.Nucleic acids research · 2025Article
- A Cell-Based Functional Assay Calibrated for Analysis ofHuman mutation · 2025Article
- Therapeutic validation of MMR-associated genetic modifiers in a human ex vivo model of Huntington disease.American journal of human genetics · 2024Article
- Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways.Nature communications · 2024Article
- The Versatile Attributes of MGMT: Its Repair Mechanism, Crosstalk with Other DNA Repair Pathways, and Its Role in Cancer.Cancers · 2024Review
- MutSα and MutSβ as size-dependent cellular determinants for prime editing in human embryonic stem cells.Molecular therapy. Nucleic acids · 2023Article
- Loss of mismatch repair promotes a direct selective advantage in human stem cells.Stem cell reports · 2022Article
- DNA repair fidelity in stem cell maintenance, health, and disease.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Functional interrogation of Lynch syndrome-associated MSH2 missense variants via CRISPR-Cas9 gene editing in human embryonic stem cells.Human mutation · 2019Article
- High Basal Levels of γH2AX in Human Induced Pluripotent Stem Cells Are Linked to Replication-Associated DNA Damage and Repair.Stem cells (Dayton, Ohio) · 2018Article
- ATR-Chk1 activation mitigates replication stress caused by mismatch repair-dependent processing of DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Does anthracycline-based chemotherapy in pregnant women with cancer offer safe cardiac and neurodevelopmental outcomes for the developing fetus?BMC cancer · 2017Review
- Genotoxic Effects of Culture Media on Human Pluripotent Stem Cells.Scientific reports · 2017Article
- Balancing self-renewal against genome preservation in stem cells: How do they manage to have the cake and eat it too?Cellular and molecular life sciences : CMLS · 2016Review
- Mitochondria in human pluripotent stem cell apoptosis.Seminars in cell & developmental biology · 2016Review
- DNA mismatch repair and the DNA damage response.DNA repair · 2016Review
- Stem cells: the pursuit of genomic stability.International journal of molecular sciences · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Human pluripotent stem cells (PSCs) are presumed to have robust DNA repair pathways to ensure genome stability. PSCs likely need to protect against mutations that would otherwise be propagated throughout all tissues of the developing embryo. How these cells respond to genotoxic stress has only recently begun to be investigated. Although PSCs appear to respond to certain forms of damage more efficiently than somatic cells, some DNA damage response pathways such as the replication stress response may be lacking. Not all DNA repair pathways, including the DNA mismatch repair (MMR) pathway, have been well characterized in PSCs to date. MMR maintains genomic stability by repairing DNA polymerase errors. MMR is also involved in the induction of cell cycle arrest and apoptosis in response to certain exogenous DNA-damaging agents. Here, we examined MMR function in PSCs. We have demonstrated that PSCs contain a robust MMR pathway and are highly sensitive to DNA alkylation damage in an MMR-dependent manner. Interestingly, the nature of this alkylation response differs from that previously reported in somatic cell types. In somatic cells, a permanent G2/M cell cycle arrest is induced in the second cell cycle after DNA damage. The PSCs, however, directly undergo apoptosis in the first cell cycle. This response reveals that PSCs rely on apoptotic cell death as an important defense to avoid mutation accumulation. Our results also suggest an alternative molecular mechanism by which the MMR pathway can induce a response to DNA damage that may have implications for tumorigenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.