Grishok A et al. (2011) Proc Natl Acad Sci U S A "Correction for Grishok et al., RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans."

Sharp PA, Grishok A, Hoersch S

[Proc Natl Acad Sci U S A, 2011]

GENETICS Correction for RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans by Alla Grishok, Sebastian Hoersch, and Phillip A. Sharp, which appeared in issue 51, December 23, 2008, of Proc Natl Acad Sci USA (105:2038620391; first published December 10, 2008; 10.1073/pnas.0810589105).The authors note that an additional affiliation for Sebastian Hoersch was omitted from the article. Sebastian Hoersch's second affiliation is Bioinformatics Group, Max Delbrck Center for Molecular Medicine, 13125 Berlin, Germany. The corrected author and affiliation lines appear below. The online version has been corrected.Alla Grishoka, Sebastian Hoerscha,b, and Phillip A. SharpaaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; and bBioinformatics Group, Max Delbrck Center for Molecular Medicine, 13125 Berlin, Germany

Alexander Van Der Linden et al. (2008) C.elegans Neuronal Development Meeting "Temperature- and Light-entrained Circadian Rhythms in C. elegans"

Sebastian Kadener, Michael Rosbash, Alexander Van Der Linden, Piali Sengupta

[C.elegans Neuronal Development Meeting, 2008]

The circadian clock is an internal timing mechanism that enables organisms to respond to, and even anticipate, changing environmental conditions associated with rotation of the earth. The output of these clocks results in circadian rhythms, which oscillate with circa 24-hr periods and control multiple aspects of behavior and physiology. Circadian rhythms can be entrained by daily environmental signals e.g. light/dark or temperature. Although circadian behaviors in C. elegans have been reported (1), no clock or clock-output genes have been identified. Homologs of animal clock genes are represented in the genome of C. elegans, but their only certain function is to regulate developmental timing. Thus, the nature, and existence of a C. elegans circadian clock remains uncertain. Since circadian transcripts exhibit rhythmic oscillations, genome-wide expression profiling is a powerful approach to identify clock and clock-output genes. We used microarrays to identify these cycling genes using temperature or light/dark as zeitgebers. Growth-synchronized populations of C. elegans were subjected to either 12:12 hr T-cycles (25:15degC) in constant darkness, or 12:12 hr photocycles at constant temperature. In order to identify 24-hr periodic gene expression, we determined the 24-hr spectral power and the probability of observing an equivalent or higher score from randomly permutated data. First, we find that in a 5-d dataset of temperature entrainment, T-cycles show a broad impact on global 24-hr periodicity (1900 transcripts, p0.02). This result can be explained by either a temperature-driven clock-independent effect or by a temperature-entrained clock-dependent effect. To distinguish between these two possibilities, we analyzed a 6-d data set combining 3-d of temperature entrainment and 3-d of subsequent constant free-running conditions, and find at least 148 temperature-entrained circadian transcripts (p0.02). Second, we identified a significant set of candidate light-entrained transcripts. Expression data from qRT-PCR suggests that these genes may represent bona fide cycling genes. Our results indicate that T-cycles directly evoke a global expression response broader than photocycles, and that a subset undergo cycling in a circadian manner. Since it is likely that the molecular components of the C. elegans clock are distinct from those of other organisms, C. elegans provides a new system for understanding circadian clocks as well as the evolution of circadian mechanisms.

Sebastian Greiss et al. (2006) European Worm Meeting "Novel Genes Specifically Affecting DNA Damage Induced Apoptosis Define Pathways Acting Upstream and Downstream of cep-1/p53"

Aymeric Bailly, Sebastian Greiss, Julie Boerckel, Shawn Ahmed, Anton Gartner

[European Worm Meeting, 2006]

Sebastian Greiss1, Aymeric Bailly1, Julie Boerckel2, Shawn Ahmed2, Anton Gartner1. Failure to properly respond to DNA damage is implicated in tumorigenesis and a number of genetic instability disorders. As part of the DNA damage response, checkpoint pathways are needed to detect DNA damage and relay a signal that elicits cell cycle arrest as well as DNA repair and/or programmed cell death. While it is known that the transcriptional induction of egl-1 by the C. elegans p53 homologue cep-1 is required for the subsequent activation of the core apoptotic machinery, the signaling network connecting damage sensing and the cell death machinery remains ill-defined. To further our understanding of the pathways leading to DNA damage induced apoptosis we pursue both candidate gene and forward genetic approaches. By scanning a series of mutations in candidate genes we found the C. elegans sirtuin sir-2.1, a NAD+ dependent protein deacetylase and homologue of yeast Sir2p to be required for DNA damage induced apoptosis, while other DNA damage responses and developmental apoptosis were at wild type levels. Furthermore, elevated levels of germ cell apoptosis in ced-9(n1653ts) and gla-1(op234) mutants were not suppressed by mutations in sir-2.1, indicating that germ cells are in principle able to undergo apoptosis. To address where sir-2.1 might act in the DNA damage pathway, we assayed the irradiation dependent transcriptional induction of the cep-1 target egl-1, which we found to be at wild type levels. These results indicate a role for sir-2.1 in activating the core apoptotic machinery downstream or in parallel to egl-1 induction, yet upstream of CED-3 activation. To help us further define the function of sir-2.1 in DNA damage induced apoptosis we have generated antibodies against sir-2.1 and are currently generating antibodies against the C. elegans core cell death components.. Our finding that pathways leading to DNA damage induced apoptosis are more complex than previously anticipated were further corroborated by finding 5 mutants not allelic to either cep-1 or sir-2.1 but also defective exclusively in DNA damage induced apoptosis. Out of these only one is unable to induce egl-1 in response to irradiation. Interestingly, two of the mutants, yp23 and yp51, interact genetically with cep-1 as cep-1/+; yp23/+ and cep-1/+; yp51/+ double heterozygotes show a dramatic reduction in DNA damage induced apoptosis. We are currently mapping those mutants.