Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis as an ancient function of the p53 family
- Equal contributors
1 Wellcome Trust Centre for Gene Regulation and Expression, School of Life Sciences, The University of Dundee, Dow Street, Dundee DD1 5EH, UK
2 MGC Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands
3 Sanofi-Aventis Deutschland GmbH, Scientific and Medical Affairs, Biological Sciences Department, Industriepark Hoechst, Bldg. G879, Room 020, D-65926 Frankfurt am Main, Germany
4 Sanofi-Aventis U.S., Scientific and Medical Affairs, Biological Sciences Department, 270 Albany St, Cambridge, MA, 02139, USA
BMC Genomics 2008, 9:334 doi:10.1186/1471-2164-9-334Published: 15 July 2008
In contrast to the three mammalian p53 family members, p53, which is generally involved
in DNA damage responses, and p63 and p73 which are primarily needed for developmental
regulation, cep-1 encodes for the single
Examining C. elegans expression profiles using whole genome Affymetrix GeneChip arrays, we found that 83 genes were induced more than two fold upon ionizing radiation (IR). None of these genes, with exception of an ATP ribosylase homolog, encode for known DNA repair genes. Using two independent cep-1 loss of function alleles we did not find genes regulated by cep-1 in the absence of IR. Among the IR-induced genes only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans specific gene. The majority of IR-induced genes appear to be involved in general stress responses, and qRT-PCR experiments indicate that they are mainly expressed in somatic tissues. Interestingly, we reveal an extensive overlap of gene expression changes occurring in response to DNA damage and in response to bacterial infection. Furthermore, many genes induced by IR are also transcriptionally regulated in longevity mutants suggesting that DNA damage and aging induce an overlapping stress response.
We performed genome-wide gene expression analyses which indicate that only a surprisingly small number of genes are regulated by CEP-1 and that DNA damage induced apoptosis via the transcriptional induction of BH3 domain proteins is likely to be an ancient DNA damage response function of the p53 family. Interestingly, although the apoptotic response to DNA damage is regulated through the transcriptional activity of CEP-1, other DNA damage responses do not appear to be regulated on the transcriptional level and do not require the p53 like gene cep-1.