title: Interstrand crosslink-induced radials form between non-homologous chromosomes, but are absent in sex chromosomes.
abstract: Fanconi anemia (FA) and cells lacking functional BRCA1 and BRCA2 proteins are hypersensitive to interstrand crosslinking (ICL) agents and show increased numbers of chromosomal breaks and radials. Although radial formation has been used to diagnose FA for more than 30 years, there has been little analysis of these characteristic formations. In this study, radials were analyzed from FA-A and FA-G fibroblasts as well as normal and retrovirally-corrected FA-A fibroblasts treated with high doses of ICLs. Radials were found to only involve non-homologous chromosome interactions and to be distributed nearly randomly along the length of chromosomes. Sites on chromosomes that did show increased frequency of radial involvement did not correlate with known fragile sites or pericentric regions. Hybrid radials were observed between mouse and human chromosomes in human-mouse hybrid cells produced by microcell-mediated chromosome transfer of mouse chromosomes into human FA-A fibroblasts. Both X and Y chromosomes were notably not involved in radials. These observations suggest that ICL repair may involve short stretches of homology, resulting in aberrant radial formation in the absence of FA proteins.
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health & Science University, MP350, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Amy E Hanlon
authors.initials: AE
authors.lastname: Newell
authors.forename: Yassmine M N
authors.initials: YM
authors.lastname: Akkari
authors.forename: Yumi
authors.initials: Y
authors.lastname: Torimaru
authors.forename: Andrew
authors.initials: A
authors.lastname: Rosenthal
authors.forename: Carol A
authors.initials: CA
authors.lastname: Reifsteck
authors.forename: Barbara
authors.initials: B
authors.lastname: Cox
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
authors.forename: Susan B
authors.initials: SB
authors.lastname: Olson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D033481:Chromosomes, Mammalian / Q000187:drug effects* / Q000235:genetics; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D051379:Mice; D012689:Sequence Homology, Nucleic Acid; D012730:Sex Chromosomes / Q000187:drug effects* / Q000235:genetics
chemical_list: D003432:Cross-Linking Reagents