title: Double-strand breaks and the concept of short- and long-term epigenetic memory.
abstract: Double-strand breaks represent an extremely cytolethal form of DNA damage and thus pose a serious threat to the preservation of genetic and epigenetic information. Though it is well-known that double-strand breaks such as those generated by ionising radiation are among the principal causative factors behind mutations, chromosomal aberrations, genetic instability and carcinogenesis, significantly less is known about the epigenetic consequences of double-strand break formation and repair for carcinogenesis. Double-strand break repair is a highly coordinated process that requires the unravelling of the compacted chromatin structure to facilitate repair machinery access and then restoration of the original undamaged chromatin state. Recent experimental findings have pointed to a potential mechanism for double-strand break-induced epigenetic silencing. This review will discuss some of the key epigenetic regulatory processes involved in double-strand break (DSB) repair and how incomplete or incorrect restoration of chromatin structure can leave a DSB-induced epigenetic memory of damage with potentially pathological repercussions.
authors.affiliation: Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 75 Commercial Road, Melbourne, Victoria, Australia.
authors.forename: Christian
authors.initials: C
authors.lastname: Orlowski
authors.forename: Li-Jeen
authors.initials: LJ
authors.lastname: Mah
authors.forename: Raja S
authors.initials: RS
authors.lastname: Vasireddy
authors.forename: Assam
authors.initials: A
authors.lastname: El-Osta
authors.forename: Tom C
authors.initials: TC
authors.lastname: Karagiannis
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D044127:Epigenesis, Genetic / Q000528:radiation effects; D020868:Gene Silencing; D006801:Humans
chemical_list: D002843:Chromatin