Homologous recombination is required for genome stability in the absence of DOG-1 in Caenorhabditis elegans.
In C. elegans, DOG-1 prevents deletions that initiate in polyG/polyC tracts (G/C tracts), most likely by unwinding secondary structures that can form in G/C tracts during lagging-strand DNA synthesis. We have used the dog-1 mutant to assay the in vivo contribution of various repair genes to the maintenance of G/C tracts. Here we show that DOG-1 and the BLM ortholog, HIM-6, act synergistically during replication; simultaneous loss of function of both genes results in replicative stress and an increase in the formation of small deletions that initiate in G/C tracts. Similarly, we demonstrate that the C. elegans orthologs of the homologous recombination repair genes BARD1, RAD51, and XPF and the trans-lesion synthesis polymerases poleta and polkappa contribute to the prevention of deletions in dog-1 mutants. Finally, we provide evidence that the small deletions generated in the dog-1 background are not formed through homologous recombination, nucleotide excision repair, or nonhomologous end-joining mechanisms, but appear to result from a mutagenic repair mechanism acting at G/C tracts. Our data support the hypothesis that absence of DOG-1 leads to replication fork stalling that can be repaired by deletion-free or deletion-prone mechanisms.
Youds
Jillian L
JL
Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
O'Neil
Nigel J
NJ
Rose
Ann M
AM
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000648:ultrastructure; D004265:DNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D017238:Genes, Helminth; D049751:Genome, Helminth; D042822:Genomic Instability; D008938:Mitosis; D008957:Models, Genetic; D009154:Mutation; D034622:RNA Interference; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D017384:Sequence Deletion; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
C438244:CEP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; C487047:HIM-6 protein, C elegans; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C491164:brd-1 protein, C elegans; D044767:Ubiquitin-Protein Ligases; D051135:Rad51 Recombinase; C495148:rad-51 protein, C elegans; D004259:DNA-Directed DNA Polymerase; D004265:DNA Helicases; C464789:Dog-1 protein, C elegans