title: Chromatin structure in double strand break repair.
abstract: Cells are under constant assault by endogenous and environmental DNA damaging agents. DNA double strand breaks (DSBs) sever entire chromosomes and pose a major threat to genome integrity as a result of chromosomal fragment loss or chromosomal rearrangements. Exogenous factors such as ionizing radiation, crosslinking agents, and topoisomerase poisons, contribute to break formation. DSBs are associated with oxidative metabolism, form during the normal S phase, when replication forks collapse and are generated during physiological processes such as V(D)J recombination, yeast mating type switching and meiosis. It is estimated that in mammalian cells ∼10 DSBs per cell are formed daily. If left unrepaired DSBs can lead to cell death or deregulated growth, and cancer development. Cellular response to DSB damage includes mechanisms to halt the progression of the cell cycle and to restore the structure of the broken chromosome. Changes in chromatin adjacent to DNA break sites are instrumental to the DNA damage response (DDR) with two apparent ends: to control compaction and to bind repair and signaling molecules to the lesion. Here, we review the key findings related to each of these functions and examine their cross-talk.
authors.affiliation: Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 21, 1113 Sofia, Bulgaria. Electronic address: agg@bio21.bas.bg.
authors.forename: Anastas
authors.initials: A
authors.lastname: Gospodinov
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002843:Chromatin / Q000378:metabolism* / Q000648:ultrastructure*; D042002:Chromatin Assembly and Disassembly; D019457:Chromosome Breakage; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D011499:Protein Processing, Post-Translational; D059767:Recombinational DNA Repair
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones
keywords: Cancer; Chromatin; DNA repair; DSBs; Histone modifications