title: CHL-1 provides an essential function affecting cell proliferation and chromosome stability in Caenorhabditis elegans.
abstract: A family of helicases that are important in maintaining genome stability is the iron-sulfur group. Members of this family include DOG-1/FANCJ, RTEL1, XPD and Chl1p/DDX11. In Caenorhabitis elegans, the predicted gene M03C11.2 has orthology to the CHL1 (Chromosome loss 1) gene in Saccharomyces cerevisiae and DDX11 (DEAD/H box polypeptide 11) in humans. In this paper, we show that the chl-1 gene in C. elegans is required for normal development and fertility. Mutants have lineage-independent cell proliferation defects that result in a Stu (sterile uncoordinated) phenotype, characterized by gonadal abnormalities and a reduced number of D motor neurons and seam cells. A chromosome stability defect is present in the germ cells, where an abnormal number of DAPI-staining chromosomes appear in diakinesis. CHL-1 function is required for the integrity of poly-guanine/poly-cytosine DNA in the absence of DOG-1/FANCJ: the loss of CHL-1 alone does not result in the deletion of G-tracts, but it does increase the number of deletions observed in the dog-1; chl-1 double mutant, indicating a role for CHL-1 during replication and repair. In addition, we observed that cohesin defects increased the number of deletions in the absence of DOG-1/FANCJ. Our results demonstrate a role for CHL-1 in cell proliferation and maintaining normal chromosome numbers, and implicate CHL-1 in chromosome stability and repair of unresolved secondary structures during replication.
authors.affiliation: Department of Medical Genetics, University of British Columbia, 419-2125 East Mall, Vancouver, BC, V6T 1Z4, Canada. gchchung@interchange.ubc.ca
authors.forename: George
authors.initials: G
authors.lastname: Chung
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: O'Neil
authors.forename: Ann M
authors.initials: AM
authors.lastname: Rose
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D023061:Gene Order; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010802:Phylogeny; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D000097722:Cohesins
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D053487:DEAD-box RNA Helicases; D004265:DNA Helicases; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C066751:CHL1 protein, S cerevisiae; C570291:CHL-1 protein, C elegans; C464789:Dog-1 protein, C elegans; C101830:DDX11 protein, human