title: C. elegans: a model of Fanconi anemia and ICL repair.
abstract: Fanconi anemia (FA) is a severe recessive disorder with a wide range of clinical manifestations [M. Levitus, H. Joenje, J.P. de Winter, The Fanconi anemia pathway of genomic maintenance, Cell Oncol. 28 (2006) 3-29]. In humans, 13 complementation groups have been identified to underlie FA: A, B, C, D1, D2, E, F, G, I, J, L, M, and N [W. Wang, Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins, Nat. Rev. Genet. 8 (2007) 735-748]. Cells defective for any of these genes display chromosomal aberrations and sensitivity to DNA interstrand cross-links (ICLs). It has therefore been suggested that the 13 FA proteins constitute a pathway for the repair of ICLs, and that a deficiency in this repair process causes genomic instability leading to the different clinical phenotypes. However, the exact nature of this repair pathway, or even whether all 13 FA proteins are involved at some stage of a linear repair process, remains to be defined. Undoubtedly, the recent identification and characterisation of FA homologues in model organisms, such as Caenorhabditis elegans, will help facilitate an understanding of the function of the FA proteins by providing new analytical tools. To date, sequence homologues of five FA genes have been identified in C. elegans. Three of these homologues have been confirmed: brc-2 (FANCD1/BRCA2), fcd-2 (FANCD2), and dog-1 (FANCJ/BRIP1); and two remain to be characterised: W02D3.10 (FANCI) and drh-3 (FANCM). Here we review how the nematode can be used to study FA-associated DNA repair, focusing on what is known about the ICL repair genes in C. elegans and which important questions remain for the field.
authors.affiliation: DNA Damage Response laboratory, London Research Institute, Cancer Research UK, Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK.
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Youds
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Barber
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Boulton
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004260:DNA Repair; D005199:Fanconi Anemia / Q000235:genetics*; D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism; D042822:Genomic Instability; D023421:Models, Animal
chemical_list: D003432:Cross-Linking Reagents; D051856:Fanconi Anemia Complementation Group Proteins