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Nucleic Acids Res. 2017 Dec 15;45(22):12625-12637. doi: 10.1093/nar/gkx1128.

Meta-analysis of DNA double-strand break response kinetics.

Author information

1
Department of Medical Biology and Laboratory of Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
2
Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.

Abstract

Most proteins involved in the DNA double-strand break response (DSBR) accumulate at the damage sites, where they perform functions related to damage signaling, chromatin remodeling and repair. Over the last two decades, studying the accumulation of many DSBR proteins provided information about their functionality and underlying mechanisms of action. However, comparison and systemic interpretation of these data is challenging due to their scattered nature and differing experimental approaches. Here, we extracted, analyzed and compared the available results describing accumulation of 79 DSBR proteins at sites of DNA damage, which can be further explored using Cumulus (http://www.dna-repair.live/cumulus/)-the accompanying interactive online application. Despite large inter-study variability, our analysis revealed that the accumulation of most proteins starts immediately after damage induction, occurs in parallel and peaks within 15-20 min. Various DSBR pathways are characterized by distinct accumulation kinetics with major non-homologous end joining proteins being generally faster than those involved in homologous recombination, and signaling and chromatin remodeling factors accumulating with varying speeds. Our meta-analysis provides, for the first time, comprehensive overview of the temporal organization of the DSBR in mammalian cells and could serve as a reference for future mechanistic studies of this complex process.

PMID:
29182755
PMCID:
PMC5728399
DOI:
10.1093/nar/gkx1128
[Indexed for MEDLINE]
Free PMC Article

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