Chromatin repair

Thoma, F. (1999). Light and dark in chromatin repair Repair of UV-induced DNA lesions by photolyase and nucleotide excision repair. EMBO J. 18, 6585-6598. 

The core unit of the chromatin, the nucleosome, consists of histones arranged as an octamer consisting of a (H3/ H4)2-tetramer complexed with two histone H2A/H2B dimers. Accessibility to DNA-binding proteins (for replication, repair, or transcription) is achieved by posttranslational modifications of the amino-termini of the histones, the histone tails phosphorylation, acetylation, methylation, ubiquitination, and sumoyla-tion. Especially acetylation of histone tails has been linked to transcriptional activation, leading to weakened interaction of the core complexes with DNA and subsequently to decondensation of chromatin. In contrast, deacetylation leads to transcriptional repression. As mentioned above, transcriptional coactivators either possess HAT activity or recruit HATs. HDACs in turn act as corepressors. 

In the nuclei of all eukaryotic cells, DNA is tightly wrapped around an octamer of histone proteins and is compacted into a dense structure known as chromatin. In order to access the genetic information which is required in numerous essential cellular processes including DNA replication, gene expression and DNA repair, chromatin needs to be partially unwound. One important mechanism to regulate chromatin structure and thus to control the access of the genomic DNA is through histone modifications [1-6]. The histone octamer is composed of two copies of H2A, H2B, H3 and H4 core histone proteins. Their tails, that protrude out of the surface of the... 

The particular sites to which the B[a]P becomes attached in the DNA will probably greatly influence its role. This may be especially important if the adduct functions directly rather than through a nonspecific, indirect process, such as induction of DNA repair. Efforts have been made to determine the specific sites to which BtalP becomes bound (92.94) and its distribution on chromatin (97,98). 

Nickel chloride has been reported to induce DNA strand breaks in CHO cells [435] in a concentration, which did not significantly injure normal cellular division, and DNA-protein cross-links, which were concentration- and time-dependent and preferentially occurred in cells in the late S phase of the cell cycle [436], The nickel cross-linked proteins included nonhistone chromatin proteins, nonhistone DNA-binding proteins and a 30 kDa protein that comigrated electrophoretically with histone HI. Moreover, blocking of cell growth in S phase [249] and induction of DNA repair synthesis in CHO cells [437] and reduction in the fidelity of DNA synthesis [438, 439], have been reported. 

J. H., Hoogerbrugge, J. W., Vreeberg, M. T. M., Baarends, W. M., Bootsma, D., Grootegoed, j. A., and Hoeijmakers, j. H. j. Inactivation of the HR6B ubiquitin-conjugating DNA repair enzyme in mice causes male sterility associated with chromatin modification. Cdl 1996, 86, 799-810. 

How does PARP-Fs role as a nucleosome-binding protein and modulator of chromatin structure, which is evident under normal physiological conditions, impact PARP-1-dependent DNA repair, cell death, and inflammatory response pathways, which occur under pathophysiological conditions A number of different scenarios are possible. For example, PARP-l s chromatin-dependent activities may be critical for its function as a DNA repair protein, since the repair of genomic DNA must occur in the context of chromatin. In addition, nucleosome-stimulated autoPARylation may play a role in depleting cellular NAD+ pools in response to cellular stresses. Furthermore, PARP-Fs chromatin-dependent activities may help to regulate the expression of immune and inflammatory response genes. These possibilities will need to be examined in the future. 

In yeast, H2A.X is dephosphorylated by the phosphatase PPH3p after it has been released from chromatin. The release of y-H2A.X from repaired chromatin is independent of DNA replication, and it therefore must be assumed that a chromatin remodeling complex actively exchanges 7-H2A.X from nucleosomes. Thus far, several candidate remodeling complexes have been identified that specifically target nucleosomes containing 7-H2A.X. 

Drabent B, Saftig P, Bode C, Doenecke D (2000) Spermatogenesis proceeds normally in mice widiout linker histone Hit. Histochem Cell Biol 113 433-442 Drabent B, Benavente R, Hoyer-Fender S (2003) Histone Hit is not replaced by Hl.l or H1.2 in pachytene spermatocytes or spermatids of Hit-deficient mice. Cytogenet Genome Res 103 307—313 Ehrenhofer-Murray AE (2004) Chromatin dynamics at DNA replication, transcription and repair. Eur J Biochem 271 2335-2349... 

Sensing DNA damage is essential for maintenance of genomic integrity and cell cycle progression. DNA repair is the second major site of DNA synthesis in a cell after replication and it involves chromatin assembly after efficient repair process. In yeast, the histone chaperone CAF-1 (chromatin Assembly factorl) mediates histone H3-H4 assembly on to newly replicated DNA and also mediates nucleotide... 

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