Radiation-induced DNA damage and chromatin structure

DNA lesions induced by ionizing radiation in cells are clustered and not ra ndomly distributed, For low linear energy transfer (LET) radiation this clu stering occurs mainly on the small scales of DNA molecules and nucleosomes, For example, experimental evidence suggests that both strands of DNA on th e nucleosomal surface can be damaged in single events and that this damage occurs with a 10-bp modulation because of protection by histories. For high LET radiation, clustering also occurs on a larger scale and depends on chr omatin organization. A particularly significant clustering occurs when an i onizing particle traverses the 30 nm chromatin fiber with generation of hea vily damaged DNA regions with an average size of about 2 kbp. On an even la rger scale, high LET radiation can produce several DNA double-strand breaks in closer proximity than expected from randomness. It is suggested that th is increases the probability of misrejoining of DNA ends and generation of lethal chromosome aberrations.