Journal
DNA REPAIR
Volume 12, Issue 10, Pages 800-810Publisher
ELSEVIER
DOI: 10.1016/j.dnarep.2013.07.006
Keywords
DNA repair; Chromatin; Histone modifications; DSBs; Cancer
Categories
Funding
- National Cancer Institute (NIH), United States
- l'Association pour la Recherche sur le Cancer (ARC), France
- la Ligue Nationale Contre le Cancer, France
- Bill and Melinda Gates Foundation
- European Union [308610]
- French National Cancer Institute (INCa)
- Bulgarian National Science Fund [DMU 03/9]
- ICGEB [CRP/12/005]
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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 similar to 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. (C). 2013 Elsevier B.V. All rights reserved.
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