The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Drosophila melanogaster MNK/Chk2 and p53 Regulate Multiple DNA Repair and Apoptotic Pathways following DNA Damage
Open accessAbstract
We have used genetic and microarray analysis to determine how ionizing radiation (IR) induces p53-dependent transcription and apoptosis in Drosophila melanogaster. IR induces MNK/Chk2-dependent phosphorylation of p53 without changing p53 protein levels, indicating that p53 activity can be regulated without an Mdm2-like activity. In a genome-wide analysis of IR-induced transcription in wild-type and mutant embryos, all IR-induced increases in transcript levels required both p53 and the Drosophila Chk2 homolog MNK. Proapoptotic targets of p53 include hid, reaper, sickle, and the tumor necrosis factor family member EIGER: Overexpression of Eiger is sufficient to induce apoptosis, but mutations in Eiger do not block IR-induced apoptosis. Animals heterozygous for deletions that span the reaper, sickle, and hid genes exhibited reduced IR-dependent apoptosis, indicating that this gene complex is haploinsufficient for induction of apoptosis. Among the genes in this region, hid plays a central, dosage-sensitive role in IR-induced apoptosis. p53 and MNK/Chk2 also regulate DNA repair genes, including two components of the nonhomologous end-joining repair pathway, Ku70 and Ku80. Our results indicate that MNK/Chk2-dependent modification of Drosophila p53 activates a global transcriptional response to DNA damage that induces error-prone DNA repair as well as intrinsic and extrinsic apoptosis pathways.
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Cited by
The Cell–Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression
Chen, J. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026104 · Cited by 1,222
p63 and p73, the ancestors of p53
Dotsch, V., Bernassola, F., Coutandin, D., Candi, E., & Melino, G. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a004887 · Cited by 326
Retrotransposon activation contributes to neurodegeneration in a Drosophila TDP-43 model of ALS
Krug, L., Chatterjee, N., Borges-Monroy, R., Hearn, S., Liao, W.-W., Morrill, K., Prazak, L., Rozhkov, N., Theodorou, D., Hammell, M., et al. (2017) · PLOS Genetics · doi:10.1371/journal.pgen.1006635 · Cited by 201
Heterochromatic Genome Stability Requires Regulators of Histone H3 K9 Methylation
Peng, J. C., & Karpen, G. H. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000435 · Cited by 183
Genetic Control of Programmed Cell Death During Animal Development
Conradt, B. (2009) · Annual Review of Genetics · doi:10.1146/annurev.genet.42.110807.091533 · Cited by 173
Metadata
- Authors
- Brodsky, M. H., Weinert, B. T., Tsang, G., Rong, Y. S., McGinnis, N. M., Golic, K. G., Rio, D. C., & Rubin, G. M.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-02-01
- Volume
- 24
- Issue
- 3
- Pages
- 1219-1231
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2108992945
- Cited by
- 315
- References
- 10
- FWCI
- 9.84
- Type
- journal article
- Language
- en
- Open access
- green
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- Brodsky, M. H., Weinert, B. T., Tsang, G., Rong, Y. S., McGinnis, N. M., Golic, K. G., Rio, D. C., & Rubin, G. M. (2004). Drosophila melanogaster MNK/Chk2 and p53 Regulate Multiple DNA Repair and Apoptotic Pathways following DNA Damage. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.24.3.1219-1231.2004
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