Higher-Order Chromatin Structure-Dependent Repair of DNA Double-Strand Breaks: Factors Affecting Elution of DNA from Nucleoids

1998 ◽  
Vol 149 (6) ◽  
pp. 533 ◽  
Author(s):  
P. J. Johnston ◽  
S. H. MacPhail ◽  
J. P. Banáth ◽  
P. L. Olive ◽  
J. P. Banath
Keyword(s):  
Chromatin Structure ◽  
Higher Order ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Factors Affecting ◽  
Strand Breaks

Heterochromatin and the DNA damage response: the need to relaxThis paper is one of a selection of papers in a Special Issue entitled 31st Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal’s usual peer review process.

2011 ◽  
Vol 89 (1) ◽  
pp. 45-60 ◽  
Author(s):  
Kendra L. Cann ◽  
Graham Dellaire
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Chromatin Structure ◽  
Peer Review Process ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Atm Kinase ◽  
Strand Breaks ◽  
Damage Response ◽  
Chromosomal Mutations

Higher order chromatin structure has an impact on all nuclear functions, including the DNA damage response. Over the past several years, it has become increasingly clear that heterochromatin and euchromatin represent separate entities with respect to both damage sensitivity and repair. The chromatin compaction present in heterochromatin helps to protect this DNA from damage; however, when lesions do occur, the compaction restricts the ability of DNA damage response proteins to access the site, as evidenced by its ability to block the expansion of H2AX phosphorylation. As such, DNA damage in heterochromatin is refractory to repair, which requires the surrounding chromatin structure to be decondensed. In the case of DNA double-strand breaks, this relaxation is at least partially mediated by the ATM kinase phosphorylating and inhibiting the function of the transcriptional repressor KAP1. This review will focus on the functions of KAP1 and other proteins involved in the maintenance or restriction of heterochromatin, including HP1 and TIP60, in the DNA damage response. As heterochromatin is important for maintaining genomic stability, cells must maintain a delicate balance between allowing repair factors access to these regions and ensuring that these regions retain their organization to prevent increased DNA damage and chromosomal mutations.

scholarly journals DNA repair goes hip-hop: SMARCA and CHD chromatin remodellers join the break dance

2017 ◽  
Vol 372 (1731) ◽  
pp. 20160285 ◽  
Author(s):  
Magdalena B. Rother ◽  
Haico van Attikum
Keyword(s):  
Dna Repair ◽  
Posttranslational Modifications ◽  
Chromatin Structure ◽  
Hip Hop ◽  
Genome Stability ◽  
Genome Instability ◽  
Current Knowledge ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks

Proper signalling and repair of DNA double-strand breaks (DSB) is critical to prevent genome instability and diseases such as cancer. The packaging of DNA into chromatin, however, has evolved as a mere obstacle to these DSB responses. Posttranslational modifications and ATP-dependent chromatin remodelling help to overcome this barrier by modulating nucleosome structures and allow signalling and repair machineries access to DSBs in chromatin. Here we recap our current knowledge on how ATP-dependent SMARCA- and CHD-type chromatin remodellers alter chromatin structure during the signalling and repair of DSBs and discuss how their dysfunction impacts genome stability and human disease. This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.

scholarly journals Μελέτη σε επίπεδο ηλεκτρονικής μικροσκοπίας της πρωτεΐνης H2AX που αναγνωρίζει βλάβες του DNA στον ανθρώπινο καρκίνο

2008 ◽  
Author(s):  
Χαρίκλεια Μαρίνου
Keyword(s):  
Dna Repair ◽  
Ionizing Radiation ◽  
Chromatin Structure ◽  
Double Strand Breaks ◽  
Lung Fibroblasts ◽  
Similar Reaction ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Dna Double Helix ◽  
Dna Ends

Eukaryotic DNA is organized into noucleosomes and high order chromatin structure, which plays an important role in the regulation of many nuclear processes including DNA repair. The DNA within our cells is continually being exposed to DNA-damaging agents. These include ultraviolet light, natural and man-made mutagenic chemicals and reactive oxygen species generated by ionizing radiation. Of the various forms of damage that are inflicted by these mutagens, probably the most dangerous is the DNA double strand breaks (DSBs). These are generated when the two complementary strands of the DNA double helix are broken simultaneously at sites that are sufficiently close to one another that base-pairing and chromatin structure are insufficient to keep the two DNA ends juxtaposed. DSBs pose a serious threat to cell viability and genome stability and they are also generated when replication forks encounter blocking lesions. The failure to repair DSBs or misrepair can result in cell death or large-scale chromosome changes including deletions, translocations and chromosome fusions that enhance genome instability and are hallmarks of cancer cells. Cells have evolved groups of proteins that function in signaling networks that sense DSBs, arrest the cell cycle and activate DNA repair pathways. Histone H2AX is a member of the H2A histone family that differs from the other H2A histones by the presence of an evolutionary conserved C-terminal motif. The serine residue in this motif becomes rapidly phosphorylated in cells when DSBs are introduced (γ-H2AX) forming foci. These γ-H2AX foci may play an essential role in the efficient recruitment of proteins involved in the repair of the DNA DSBs. This role may be to mark the site of the damage. It is also possible that the H2AX phosphorylation alters chromatin structure to facilitate repair or to stabilize the break region so that the DNA ends remain in proximity. Given the above, the main purpose of this study was to ultrastructurally localize using immunogold, γ-H2AX foci in human lung fibroblasts irradiated with specific doses of ionizing radiation in order to create DSBs and to examine if a similar reaction takes place in cancer lung cells. The results indicate that when fibroblasts are experimentally exposed to increasing doses of radiation, aggregates of gold particles are observed indicating localization of γ-H2AX foci. In a series of similar experiments using cancer lung tissue, the same pattern of gold particle localization is observed suggesting that in these cells the formation of γ-H2AX foci is triggered. It is the first time ever that γ-H2AX foci formation is ultrastructurally identified with electron microscopy and this is very important since it confirms the existence of foci in chromatin and indicates the sites of DNA double strand breaks.

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