Copy number variants are produced in response to low-dose ionizing radiation in cultured cells

摘要: Despite their importance to human genetic variation and disease, little is known about the molecular mechanisms environmental risk factors that impact copy number variant (CNV) formation. While it clear replication stress can lead de novo CNVs, for example, following treatment of cultured mammalian cells with aphidicolin (APH) hydroxyurea (HU), effect different types mutagens on CNV induction unknown. Here we report ionizing radiation (IR) in range 1.5–3.0 Gy effectively induces mutations normal fibroblasts. These IR-induced CNVs are found throughout genome, same hotspot regions seen after APH- HU-induced stress. IR produces duplications at a higher frequency relative deletions than do APH HU. At most hotspots, these physically shifted from typically deleted or HU, suggesting pathways involved breakpoint junctions irradiated samples characterized by microhomology, blunt ends, insertions like those spontaneous APH/HU-induced nonrecurrent vivo. The similarity suggests low-dose through replication-dependent mechanism, as opposed replication-independent repair DSBs. Consistent this lower yield was observed when were held 48 hr before replating irradiation. results predict any DNA damaging agent impairs capable creating CNVs. Environ. Mol. Mutagen. 55:103–113, 2014. © 2013 Wiley Periodicals, Inc.