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Cited by 339

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 access
Koh, David W., Lawler, Ann M., Poitras, Marc F., Sasaki, Masayuki, Wattler, Sigrid, Nehls, Michael C., Stöger, Tobias, Poirier, Guy G., Dawson, Valina L., Dawson, Ted M.·2004·Proceedings of the National Academy of Sciences

Abstract

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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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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CoChat. (2026). Citation check: Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality. https://app.cochat.ai/papers/10.1073/pnas.0406182101
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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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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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