TY - JOUR
T1 - From DNA damage to chromosome aberrations
T2 - Joining the break
AU - Durante, M.
AU - Bedford, J. S.
AU - Chen, D. J.
AU - Conrad, S.
AU - Cornforth, M. N.
AU - Natarajan, A. T.
AU - van Gent, D. C.
AU - Obe, G.
N1 - Funding Information:
The 10th ISCA meeting was generously supported by the GSI Helmholtzzentrum für Schwerionenforschung (Darmstadt, Germany) , and the International Association for Radiation Research (IARR) . The authors wish to thank Gisela Taucher-Scholz and Sylvia Ritter for their comments and suggestions on the manuscript, and all the colleagues who attended the Round Table and provided useful inputs and questions during the discussion.
PY - 2013/5/30
Y1 - 2013/5/30
N2 - Despite many years of experimental studies on radiation-induced chromosomal aberrations, and the recent progress in elucidating the molecular mechanisms of the DNA damage response, the link between DNA double-strand break repair and its expression as microscopically visible chromosomal rearrangements remains, in many ways, obscure. Some long standing controversies have partially been resolved to the satisfaction of most investigators, including the linearity of the dose-response for DNA double-strand break induction, the necessity of pairwise interaction of radiogenic damaged sites in the formation of exchange aberrations, and the importance of proximity between lesions in misrejoining. However, the contribution of different molecular DNA repair mechanisms (e.g., alternative end-joining pathways) and their impact on the kinetics of aberration formation is still unclear, as is the definition of "complex" radiogenic damaged sites - in either the chemical or spatial sense - which ostensibly lead to chromosome rearrangements. These topics have been recently debated by molecular biologists and cytogeneticists, whose opinions are summarized in this paper.
AB - Despite many years of experimental studies on radiation-induced chromosomal aberrations, and the recent progress in elucidating the molecular mechanisms of the DNA damage response, the link between DNA double-strand break repair and its expression as microscopically visible chromosomal rearrangements remains, in many ways, obscure. Some long standing controversies have partially been resolved to the satisfaction of most investigators, including the linearity of the dose-response for DNA double-strand break induction, the necessity of pairwise interaction of radiogenic damaged sites in the formation of exchange aberrations, and the importance of proximity between lesions in misrejoining. However, the contribution of different molecular DNA repair mechanisms (e.g., alternative end-joining pathways) and their impact on the kinetics of aberration formation is still unclear, as is the definition of "complex" radiogenic damaged sites - in either the chemical or spatial sense - which ostensibly lead to chromosome rearrangements. These topics have been recently debated by molecular biologists and cytogeneticists, whose opinions are summarized in this paper.
KW - Chromosome aberrations
KW - DNA double-strand breaks
KW - Resection
UR - http://www.scopus.com/inward/record.url?scp=84884208825&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884208825&partnerID=8YFLogxK
U2 - 10.1016/j.mrgentox.2013.05.014
DO - 10.1016/j.mrgentox.2013.05.014
M3 - Article
C2 - 23707699
AN - SCOPUS:84884208825
SN - 1383-5718
VL - 756
SP - 5
EP - 13
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
IS - 1-2
ER -