Assembly and function of DNA double-strand break repair foci in mammalian cells
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Assembly and function of DNA double-strand break repair foci in mammalian cells. / Bekker-Jensen, Simon; Mailand, Niels.
In: D N A Repair, Vol. 9, No. 12, 10.12.2010, p. 1219-28.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Assembly and function of DNA double-strand break repair foci in mammalian cells
AU - Bekker-Jensen, Simon
AU - Mailand, Niels
N1 - Copyright © 2010 Elsevier B.V. All rights reserved.
PY - 2010/12/10
Y1 - 2010/12/10
N2 - DNA double-strand breaks (DSBs) are among the most cytotoxic types of DNA damage, which if left unrepaired can lead to mutations or gross chromosomal aberrations, and promote the onset of diseases associated with genomic instability such as cancer. One of the most discernible hallmarks of the cellular response to DSBs is the accumulation and local concentration of a plethora of DNA damage signaling and repair proteins in the vicinity of the lesion, initiated by ATM-mediated phosphorylation of H2AX (¿-H2AX) and culminating in the generation of distinct nuclear compartments, so-called Ionizing Radiation-Induced Foci (IRIF). The assembly of proteins at the DSB-flanking chromatin occurs in a highly ordered and strictly hierarchical fashion. To a large extent, this is achieved by regulation of protein-protein interactions triggered by a variety of post-translational modifications including phosphorylation, ubiquitylation, SUMOylation, and acetylation. Over the last decade, insight into the identity of proteins residing in IRIF and the molecular underpinnings of their retention at these structures has been vastly expanded. Despite such advances, however, our understanding of the biological relevance of such DNA repair foci still remains limited. In this review, we focus on recent discoveries on the mechanisms that govern the formation of IRIF, and discuss the implications of such findings in light of our understanding of the physiological importance of these structures.
AB - DNA double-strand breaks (DSBs) are among the most cytotoxic types of DNA damage, which if left unrepaired can lead to mutations or gross chromosomal aberrations, and promote the onset of diseases associated with genomic instability such as cancer. One of the most discernible hallmarks of the cellular response to DSBs is the accumulation and local concentration of a plethora of DNA damage signaling and repair proteins in the vicinity of the lesion, initiated by ATM-mediated phosphorylation of H2AX (¿-H2AX) and culminating in the generation of distinct nuclear compartments, so-called Ionizing Radiation-Induced Foci (IRIF). The assembly of proteins at the DSB-flanking chromatin occurs in a highly ordered and strictly hierarchical fashion. To a large extent, this is achieved by regulation of protein-protein interactions triggered by a variety of post-translational modifications including phosphorylation, ubiquitylation, SUMOylation, and acetylation. Over the last decade, insight into the identity of proteins residing in IRIF and the molecular underpinnings of their retention at these structures has been vastly expanded. Despite such advances, however, our understanding of the biological relevance of such DNA repair foci still remains limited. In this review, we focus on recent discoveries on the mechanisms that govern the formation of IRIF, and discuss the implications of such findings in light of our understanding of the physiological importance of these structures.
KW - Animals
KW - BRCA1 Protein
KW - Cell Nucleus
KW - Chromatin
KW - DNA Breaks, Double-Stranded
KW - DNA Repair
KW - DNA-Binding Proteins
KW - Genomic Instability
KW - Guanine Nucleotide Exchange Factors
KW - Histones
KW - Humans
KW - Intracellular Signaling Peptides and Proteins
KW - Multiprotein Complexes
KW - Nuclear Proteins
KW - Phosphorylation
KW - Protein Processing, Post-Translational
KW - Trans-Activators
KW - Ubiquitin-Protein Ligases
KW - Ubiquitination
U2 - 10.1016/j.dnarep.2010.09.010
DO - 10.1016/j.dnarep.2010.09.010
M3 - Journal article
C2 - 21035408
VL - 9
SP - 1219
EP - 1228
JO - DNA Repair
JF - DNA Repair
SN - 1568-7864
IS - 12
ER -
ID: 33747855