Nematode Genetics


  HEADDr LAKOWSKI Bernard / lakowski@pasteur.fr
  MEMBERSDr GONTIJO Alisson


  Annual Report

Introduction

The Nematode Genetics group uses the power of molecular genetics in the Nematode Caenorhabditis elegans, as well as the wealth of emerging genomic information on other nematode species, to address fundamental biological questions and biological role of homologs of certain human disease genes.

Suppressor of Presenilin (spr) genes

We have generated a large collection of mutations and identified several genes that by-pass the need for the C. elegans sel-12 presenilin gene. Genetic and molecular data suggests that the SPR genes form a complex that regulates the expression of the second presenilin gene, hop-1, and presumably other targets. Several SPR proteins are similar to components of the REST-CoREST complex that represses the transcription of many of neuronal genes in non-neuronal tissues and in neuronal stem cells and plays a role in maintaining neural stem cell fate. We have found that SPR-1 encodes a clear homolog of

CoREST, the scaffold protein on which the complex assembles, while SPR-5 is a clear homolog of LSD1, a lysine specific histone demethylase. We are characterizing the known spr genes further by genetics and chromatin immunoprecipitation and trying to identify additional genes that can suppress sel-12. Recently we have cloned spr-6. Phenotypic, genetic and molecular data suggests that SPR-6 may be an additional component of the SPR complex. We have also discovered that mutations spr-8 are allelic to smg-6, a core component of the Non-sense Mediated Decay (NMD) pathway, and that other NMD genes can also weakly suppress sel-12.

The DNA helicase DOG-1

DOG-1 is the C. elegans homolog of BRIP1, a human gene mutated in rare cases of Familial Breast Cancer and in Fanconi anemia. In C. elegans, the absence of dog-1 causes genomic instability at sites surrounding Guanine rich sequences that can form G-quadruplex structures. We have been doing genetic screens for spontaneous mutations in a dog-1 background to define further the spectrum of mutations induced by dog-1. In the process we have demonstrated that the unique spectrum of mutations induced by dog-1 can be very useful for creating genetic tools and for identifying new genes. Using dog-1 we have identified 15 mutations in spr-3. We have also recovered mutations in five genes that had not previously been mutated and/or identified in forward genetic screens, which we are characterizing in collaboration with other C.elegans groups.

lakowski.jpg

Top: an egg-laying defective sel-12 hermaphrodite bloated with eggs. Bottom: a suppressed sel-12; spr-6 animal with laid eggs and young larvae.



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
If you have problems with this Web page, please write to rescom@pasteur.fr