Caenorhabditis elegans POLQ-1 and HEL-308 function in two distinct DNA interstrand cross-link repair pathways.
DNA interstrand cross-links (ICLs) are highly cytotoxic DNA lesions hindering DNA replication and transcription. Whereas in bacteria and yeast the molecular mechanisms involved in ICL repair are genetically well dissected, the scenario in multicellular organisms remains unclear. Here, we report that the two new mus308 genes, polq-1 and hel-308 are involved in ICL repair in Caenorhabditis elegans. After treatment with ICL agents, a decrease in survival and an increase in checkpoint-induced cell-cycle arrest and apoptosis of germ cells is observed in mutants of both genes. Although sensitive to ICL agents and to a minor extent to IR, cytological and epistatic analyses suggest that polq-1 and hel-308 are involved in different DNA repair pathways. While hel-308 functions in a Fanconi anemia-dependent pathway, polq-1 has a role in a novel distinct and brc-1 (CeBRCA1)-dependent ICL repair process in metazoans.
Muzzini
Diego M
DM
Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita' degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Plevani
Paolo
P
Boulton
Simon J
SJ
Cassata
Giuseppe
G
Marini
Federica
F
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D017931:DNA Primers; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D000097462:DNA Polymerase theta
D017931:DNA Primers; D004259:DNA-Directed DNA Polymerase; D000097462:DNA Polymerase theta