A genome wide RNAi-screen in C. elegans enabled the identification of genetic interaction partners of
lin-35, the homologue of the human tumor suppressor Rb (Ceron et al. 2007). Since the Rb pathway is altered or abrogated in the majority of human tumors, the examination of these interactions could be an important step in the development of anti-cancer drugs. One of the identified genes was
swsn-2.1. This gene is a homologue of the human genes SMARCD1, SMARCD2 and SMARCD3, which encode subunits of the SWI/SNF chromatin remodeling complex. We observed that
swsn-2.1 inactivation causes enhanced proliferation in certain cell lineages including the intestine. Furthermore, we have found that its human homologues show altered expression levels in colon carcinomas. Due to these preliminary observations, we chose to study
swsn-2.1 in more detail.
Two different
swsn-2.1 mutant alleles are at our disposal: one of them,
he159, was isolated in the course of a screen in a deletion library. This mutation gives rise to various abnormalities, such as protruding vulva and sterility, whereby the penetrance is temperature-dependent. The second allele,
tm3309, which we are backcrossing in our lab, was generated by the NBRP knock-out consortium. Animals that are homozygous for this mutation are arrested at early stages. We are employing these mutant alleles as well as RNAi for the functional characterization of
swsn-2.1. We are generating transgenic strains for the
swsn-2.1 gene and have recently obtained a specific antibody for SWSN-2.1 that will help as to examine its expression pattern in addition to identifying interaction partners. Moreover, we are studying the functional link between
swsn-2.1 and its paralog
swsn-2.2. Beyond that, we intend to investigate the conservation of
swsn-2.1 functions and study the implication of its human homologues in cancer development.