The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality
Open accessAbstract
The metabolism of poly(ADP-ribose) (PAR) is critical for genomic stability in multicellular eukaryotes. Here, we show that the failure to degrade PAR by means of disruption of the murine poly(ADP-ribose) glycohydrolase (PARG) gene unexpectedly causes early embryonic lethality and enhanced sensitivity to genotoxic stress. This lethality results from the failure to hydrolyze PAR, because PARG null embryonic day (E) 3.5 blastocysts accumulate PAR and concurrently undergo apoptosis. Moreover, embryonic trophoblast stem cell lines established from early PARG null embryos are viable only when cultured in medium containing the poly(ADP-ribose) polymerase inhibitor benzamide. Cells lacking PARG also show reduced growth, accumulation of PAR, and increased sensitivity to cytotoxicity induced by N -methyl- N ′-nitro- N -nitrosoguanidine and menadione after benzamide withdrawal. These results provide compelling evidence that the failure to degrade PAR has deleterious consequences. Further, they define a role for PARG in embryonic development and a protective role in the response to genotoxic stress.
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Cites
Mediation of Poly(ADP-Ribose) Polymerase-1-Dependent Cell Death by Apoptosis-Inducing Factor
Yu, S.-W., Wang, H., Poitras, M. F., Coombs, C., Bowers, W. J., Federoff, H. J., Poirier, G. G., Dawson, T. M., & Dawson, V. L. (2002) · Science · doi:10.1126/science.1072221 · Cited by 1,826
Self-citationA Role of Poly (ADP-Ribose) Polymerase in NF- B Transcriptional Activation
Hassa, P. O., & Hottiger, M. O. (1999) · Biological Chemistry · doi:10.1515/bc.1999.118 · Cited by 296
Cited by
The multifaceted roles of PARP1 in DNA repair and chromatin remodelling
Ray Chaudhuri, A., & Nussenzweig, A. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.53 · Cited by 1,786
New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs
Gibson, B. A., & Kraus, W. L. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3376 · Cited by 1,226
The PARP Side of the Nucleus: Molecular Actions, Physiological Outcomes, and Clinical Targets
Krishnakumar, R., & Kraus, W. L. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.017 · Cited by 836
PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes
Gupte, R., Liu, Z., & Kraus, W. L. (2017) · Genes & Development · doi:10.1101/gad.291518.116 · Cited by 681
“For example, the accumulation of PAR due to loss of PARG activity causes early embryonic lethality as well as increased sensitivity to genotoxic stress (Koh et al. 2004).”
BackgroundParthanatos: mitochondrial‐linked mechanisms and therapeutic opportunities
Fatokun, A. A., Dawson, V. L., & Dawson, T. M. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12416 · Cited by 594
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Metadata
- Authors
- Koh, D. W., Lawler, A. M., Poitras, M. F., Sasaki, M., Wattler, S., Nehls, M. C., Stöger, T., Poirier, G. G., Dawson, V. L., & Dawson, T. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-12-10
- Volume
- 101
- Issue
- 51
- Pages
- 17699-17704
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1997953313
- Cited by
- 339
- References
- 2
- FWCI
- 5.88
- Type
- journal article
- Language
- en
- Open access
- green
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- Koh, D. W., Lawler, A. M., Poitras, M. F., Sasaki, M., Wattler, S., Nehls, M. C., Stöger, T., Poirier, G. G., Dawson, V. L., & Dawson, T. M. (2004). Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0406182101
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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