Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387151567> ?p ?o ?g. }
Showing items 1 to 67 of
67
with 100 items per page.
- W4387151567 abstract "Abstract Although mechanisms of telomere protection are well-defined in differentiated cells, it is poorly understood how stem cells sense and respond to telomere dysfunction. In particular, the broader impact of telomeric double-strand breaks (DSBs) in these cells is poorly characterized. Here, we report on DNA damage signaling, cell cycle, and transcriptome-level changes in human induced pluripotent stem cells (iPSCs) in response to telomere-internal DSBs. We engineered human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at telomeres. Using this model, we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DDR, which leads to p53-independent cell cycle arrest in G2. Using CRISPR-Cas9 to cripple the catalytic domain of telomerase, we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres, which instead are effectively repaired by robust homologous recombination (HR). In contrast to HR-based telomere maintenance in mouse embryonic stem cells, we find neither evidence that HR causes extension of telomeres beyond their initial lengths, nor an apparent role for ZSCAN4 in this process. Rather, HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length which is compatible with sustained survival of the cells over several days of TRF1-FokI induction. Our findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric damage." @default.
- W4387151567 created "2023-09-29" @default.
- W4387151567 creator A5007648506 @default.
- W4387151567 creator A5011609263 @default.
- W4387151567 creator A5018249076 @default.
- W4387151567 creator A5057596396 @default.
- W4387151567 creator A5091021823 @default.
- W4387151567 date "2023-09-28" @default.
- W4387151567 modified "2023-09-30" @default.
- W4387151567 title "Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair" @default.
- W4387151567 doi "https://doi.org/10.1093/jmcb/mjad058" @default.
- W4387151567 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37771090" @default.
- W4387151567 hasPublicationYear "2023" @default.
- W4387151567 type Work @default.
- W4387151567 citedByCount "0" @default.
- W4387151567 crossrefType "journal-article" @default.
- W4387151567 hasAuthorship W4387151567A5007648506 @default.
- W4387151567 hasAuthorship W4387151567A5011609263 @default.
- W4387151567 hasAuthorship W4387151567A5018249076 @default.
- W4387151567 hasAuthorship W4387151567A5057596396 @default.
- W4387151567 hasAuthorship W4387151567A5091021823 @default.
- W4387151567 hasBestOaLocation W43871515671 @default.
- W4387151567 hasConcept C104317684 @default.
- W4387151567 hasConcept C107459253 @default.
- W4387151567 hasConcept C134935766 @default.
- W4387151567 hasConcept C143425029 @default.
- W4387151567 hasConcept C145103041 @default.
- W4387151567 hasConcept C153911025 @default.
- W4387151567 hasConcept C177336024 @default.
- W4387151567 hasConcept C28328180 @default.
- W4387151567 hasConcept C502942594 @default.
- W4387151567 hasConcept C54355233 @default.
- W4387151567 hasConcept C552990157 @default.
- W4387151567 hasConcept C86803240 @default.
- W4387151567 hasConcept C94581717 @default.
- W4387151567 hasConcept C95444343 @default.
- W4387151567 hasConceptScore W4387151567C104317684 @default.
- W4387151567 hasConceptScore W4387151567C107459253 @default.
- W4387151567 hasConceptScore W4387151567C134935766 @default.
- W4387151567 hasConceptScore W4387151567C143425029 @default.
- W4387151567 hasConceptScore W4387151567C145103041 @default.
- W4387151567 hasConceptScore W4387151567C153911025 @default.
- W4387151567 hasConceptScore W4387151567C177336024 @default.
- W4387151567 hasConceptScore W4387151567C28328180 @default.
- W4387151567 hasConceptScore W4387151567C502942594 @default.
- W4387151567 hasConceptScore W4387151567C54355233 @default.
- W4387151567 hasConceptScore W4387151567C552990157 @default.
- W4387151567 hasConceptScore W4387151567C86803240 @default.
- W4387151567 hasConceptScore W4387151567C94581717 @default.
- W4387151567 hasConceptScore W4387151567C95444343 @default.
- W4387151567 hasLocation W43871515671 @default.
- W4387151567 hasLocation W43871515672 @default.
- W4387151567 hasOpenAccess W4387151567 @default.
- W4387151567 hasPrimaryLocation W43871515671 @default.
- W4387151567 hasRelatedWork W146190332 @default.
- W4387151567 hasRelatedWork W189220409 @default.
- W4387151567 hasRelatedWork W1987643363 @default.
- W4387151567 hasRelatedWork W2017510302 @default.
- W4387151567 hasRelatedWork W2025559976 @default.
- W4387151567 hasRelatedWork W2037146644 @default.
- W4387151567 hasRelatedWork W2080744124 @default.
- W4387151567 hasRelatedWork W2163229747 @default.
- W4387151567 hasRelatedWork W2786040415 @default.
- W4387151567 hasRelatedWork W3200421927 @default.
- W4387151567 isParatext "false" @default.
- W4387151567 isRetracted "false" @default.
- W4387151567 workType "article" @default.