title: Single nucleotide-level mapping of DNA double-strand breaks in human HEK293T cells.
abstract: Constitutional biological processes involve the generation of DNA double-strand breaks (DSBs). The production of such breaks and their subsequent resolution are also highly relevant to neurodegenerative diseases and cancer, in which extensive DNA fragmentation has been described Stephens et al. (2011), Blondet et al. (2001). Tchurikov et al. Tchurikov et al. (2011, 2013) have reported previously that frequent sites of DSBs occur in chromosomal domains involved in the co-ordinated expression of genes. This group report that hot spots of DSBs in human HEK293T cells often coincide with H3K4me3 marks, associated with active transcription Kravatsky et al. (2015) and that frequent sites of DNA double-strand breakage are likely to be relevant to cancer genomics Tchurikov et al. (2013, 2016) . Recently, they applied a RAFT (rapid amplification of forum termini) protocol that selects for blunt-ended DSB sites and mapped these to the human genome within defined co-ordinate 'windows'. In this paper, we re-analyse public RAFT data to derive sites of DSBs at the single-nucleotide level across the built genome for human HEK293T cells (https://figshare.com/s/35220b2b79eaaaf64ed8). This refined mapping, combined with accessory ENCODE data tracks and ribosomal DNA-related sequence annotations, will likely be of value for the design of clinically relevant targeted assays such as those for cancer susceptibility, diagnosis, treatment-matching and prognostication.
authors.affiliation: Victorian Life Sciences Computation Initiative, The University of Melbourne, Australia.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Pope
authors.affiliation: Victorian Life Sciences Computation Initiative, The University of Melbourne, Australia.
authors.forename: Khalid
authors.initials: K
authors.lastname: Mahmood
authors.affiliation: Victorian Life Sciences Computation Initiative, The University of Melbourne, Australia.
authors.forename: Chol-Hee
authors.initials: CH
authors.lastname: Jung
authors.affiliation: Victorian Life Sciences Computation Initiative, The University of Melbourne, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Georgeson
authors.affiliation: Victorian Life Sciences Computation Initiative, The University of Melbourne, Australia; Genomic Technologies Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Park
keywords: Double-strand breaks; Forum domains; Fragile sites; HEK293T; Human genome