PARP is important for genomic stability but dispensable in apoptosis
1997 (English)In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 11, no 18, 2347-2358 p.Article in journal (Refereed) Published
Mice lacking the gene encoding poly(ADP-ribosyl) transferase (PARP or ADPRT) display no phenotypic abnormalities, although aged mice are susceptible to epidermal hyperplasia and obesity in a mixed genetic background. Whereas embryonic fibroblasts lacking PARP exhibit normal DNA excision repair, they grow more slowly in vitro. Here we investigated the putative roles of PARP in cell proliferation, cell death, radiosensitivity, and DNA recombination, as well as chromosomal stability. We show that the proliferation deficiency in vitro and in vive is most likely caused by a hypersensitive response to environmental stress. Although PARP is specifically cleaved during apoptosis, cells Backing this molecule apoptosed normally in response to treatment with anti-Fas, tumor neurosis factor alpha, gamma-irradiation, and dexamethasone, indicating that PARP is dispensable in apoptosis and that PARP-/-thymocytes are not hypersensitive to ionizing radiation. Furthermore, the capacity of mutant cells to carry out immunoglobulin class switching and V(D)J recombination is normal. Finally, primary PARP mutant fibroblasts and splenocytes exhibited an elevated frequency of spontaneous sister chromatid exchanges and elevated micronuclei formation after treatment with genotoxic agents, establishing an important role for PARP in the maintenance of genomic integrity.
Place, publisher, year, edition, pages
Cold Spring Harbor Laboratory Press (CSHL), 1997. Vol. 11, no 18, 2347-2358 p.
adp-ribosylation, aggregation of embryos, antisense rna expression, Apoptosis, dna-repair, gamma-irradiation, ice/ced-3 protease, involvement, mammalian-cells, PARP inactivation, poly(adp-ribose) polymerase-activity, recombination, sister chromatid exchange, stress response, transdominant inhibition
Biochemistry and Molecular Biology Cell Biology Genetics
IdentifiersURN: urn:nbn:se:liu:diva-87071DOI: 10.1101/gad.11.18.2347ISI: A1997XX74800004PubMedID: 9308963OAI: oai:DiVA.org:liu-87071DiVA: diva2:584802