Chromatin structure and radiation-induced DNA damage: from structural biology to radiobiology.
Genomic DNA in eukaryotic cells is basically divided into chromosomes, each consisting of a single huge nucleosomal fiber. It is now clear that chromatin structure and dynamics play a critical role in all processes involved in DNA metabolism, e.g. replication, transcription, repair and recombination. Radiation is a useful tool to study the biological effects of chromatin alterations. Conversely, radiotherapy and radiodiagnosis raise questions about the influence of chromatin integrity on clinical features and secondary effects. This review focuses on the link between DNA damage and chromatin structure at different scales, showing how a comprehensive multiscale vision is required to understand better the effect of radiations on DNA. Clinical aspects related to high- and low-dose of radiation and chromosomal instability will be discussed. At the same time, we will show that the analysis of the radiation-induced DNA damage distribution provides good insight on chromatin structure. Hence, we argue that chromatin "structuralists" and radiobiological "clinicians" would each benefit from more collaboration with the other. We hope that this focused review will help in this regard.
Genome Structure and Instability, National Museum of Natural History, Paris, France; CNRS UMR7196, Paris, France; INSERM U1154, Paris, France; Nuclear Architecture and Dynamics, CNRS GDR 3536, Paris, France. Electronic address: lavelle@mnhn.fr.
Christophe
C
Lavelle
Nuclear Architecture and Dynamics, CNRS GDR 3536, Paris, France; INSERM, UMR1052, Radiobiology Group, Cancer Research Centre of Lyon, Lyon, France.
Nicolas
N
Foray
D002843:Chromatin / Q000235:genetics / Q000528:radiation effects*; D043171:Chromosomal Instability / Q000235:genetics / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009707:Nucleosomes / Q000235:genetics / Q000528:radiation effects*; D011839:Radiation, Ionizing; D011853:Radiobiology / Q000379:methods / Q000639:trends
D002843:Chromatin; D009707:Nucleosomes
Chromatin; DNA damage; Nucleosome; Radiation; Radiobiology