Psoralen Photobiology: The Relationship Between DNA Damage, Chromatin Structure, Transcription, and Immunogenic Effects

Author(s):  
F. P. Gasparro ◽  
A. Felli ◽  
I. M. Schmitt
Genetics ◽  
2002 ◽  
Vol 160 (4) ◽  
pp. 1375-1387
Author(s):  
Emmanuelle M D Martini ◽  
Scott Keeney ◽  
Mary Ann Osley

Abstract To investigate the role of the nucleosome during repair of DNA damage in yeast, we screened for histone H2B mutants that were sensitive to UV irradiation. We have isolated a new mutant, htb1-3, that shows preferential sensitivity to UV-C. There is no detectable difference in bulk chromatin structure or in the number of UV-induced cis-syn cyclobutane pyrimidine dimers (CPD) between HTB1 and htb1-3 strains. These results suggest a specific effect of this histone H2B mutation in UV-induced DNA repair processes rather than a global effect on chromatin structure. We analyzed the UV sensitivity of double mutants that contained the htb1-3 mutation and mutations in genes from each of the three epistasis groups of RAD genes. The htb1-3 mutation enhanced UV-induced cell killing in rad1Δ and rad52Δ mutants but not in rad6Δ or rad18Δ mutants, which are defective in postreplicational DNA repair (PRR). When combined with other mutations that affect PRR, the histone mutation increased the UV sensitivity of strains with defects in either the error-prone (rev1Δ) or error-free (rad30Δ) branches of PRR, but did not enhance the UV sensitivity of a strain with a rad5Δ mutation. When combined with a ubc13Δ mutation, which is also epistatic with rad5Δ, the htb1-3 mutation enhanced UV-induced cell killing. These results suggest that histone H2B acts in a novel RAD5-dependent branch of PRR.


1986 ◽  
Vol 6 (8) ◽  
pp. 3014-3017 ◽  
Author(s):  
D S Pederson ◽  
K Shupe ◽  
G A Bannon ◽  
M A Gorovsky

The relationship between chromatin structure and the transcriptional activity of the histone H4-I gene of Tetrahymena thermophila was explored. Indirect end-labeling studies demonstrated that major DNase I- and micrococcal nuclease-hypersensitive sites flank the active macronuclear genes but not the inactive micronuclear genes. Runon transcription experiments with isolated macronuclei indicated that histone gene transcription rates decreased when cells were starved. However, macronuclear nuclease-hypersensitive sites persisted upon starvation. Thus, one level of transcriptional control of the H4-I gene results in altered chromatin structure and is established during nuclear differentiation. The rate of transcription is also controlled, but not through hypersensitive site-associated structures.


2010 ◽  
Vol 70 (4 suppl) ◽  
pp. 1223-1230 ◽  
Author(s):  
C. Rechenmacher ◽  
AM. Siebel ◽  
A. Goldoni ◽  
CR. Klauck ◽  
T. Sartori ◽  
...  

The aim of this study was to determine the feasibility of combining water quality analysis with different biomarkers to characterise the relationship between anthropogenic contamination and biotic response in the Sinos River, southern Brazil. Wistar rats were studied using three biomarkers combined with physical, chemical and microbiological analysis to assess the effects of pollution at four sampling sites. The induction of oxidative stress was quantified by MDA levels in peripheral blood, lymphocyte DNA damage was determined using the comet assay, and histopathological changes were analysed in the liver. After sampling, animals were allowed to drink the river water during a 48 hours period. No increase in oxidative stress and DNA damage was observed. However, liver damage was observed in the animals exposed to water samples, indicating that the Sinos River is contaminated with hepatotoxic substances. Water analyses confirmed that water quality decreased downriver.


2020 ◽  
Author(s):  
Aimei Liu ◽  
Feng Zhu ◽  
Xiaohui Zhu ◽  
Yulian Wang ◽  
Awais Ihsan ◽  
...  

Abstract Background: Cyadox is an effective growth-promoting antibiotic, which is similar to the role of recombinant growth hormone (rGH). Current studies have shown that cyadox can promote animal growth through altering intestinal microflora, improving protein utilization and increasing protein synthesis. Increasing evidence suggests that epigenetics are also closely related to growth. However, the potential role of epigenetics in the cyadox for growth has not been explored. Results: Here, we used recombinant growth hormone (rGH) and cyadox to study the relationship between growth and changes in epigenetics including DNA methylation, histone modification and chromatin structure. Bisulfite DNA sequencing (BSP) assay suggested that cyadox and rGH treatments increased IGF-1 expression partially by hypomethylation at CpG sites within the promoter region of IGF-1, which was regulated by DNA methyltransferases (DNMTs). We also observed an enrichment of H3K4me3 and H3K27ac at the promoter regions of IGF-1 by ChIP-qPCR assay, which contributed to an increase in IGF-1 transcription. In addition, immunofluorometric assay displayed cellular accessible chromatin structure following the treatment of cyadox and rGH, facilitating the combination of transcription factors and DNA and thus enhancing gene transcription. Conclusions: Taken together, our findings indicated that cyadox and rGH promote cell growth partially through epigenetic changes, providing a prospect for the development of animal growth-promoting drugs in the future.


2016 ◽  
Vol 94 (5) ◽  
pp. 381-395 ◽  
Author(s):  
Poonam Agarwal ◽  
Kyle M. Miller

DNA damage occurs within the chromatin environment, which ultimately participates in regulating DNA damage response (DDR) pathways and repair of the lesion. DNA damage activates a cascade of signaling events that extensively modulates chromatin structure and organization to coordinate DDR factor recruitment to the break and repair, whilst also promoting the maintenance of normal chromatin functions within the damaged region. For example, DDR pathways must avoid conflicts between other DNA-based processes that function within the context of chromatin, including transcription and replication. The molecular mechanisms governing the recognition, target specificity, and recruitment of DDR factors and enzymes to the fundamental repeating unit of chromatin, i.e., the nucleosome, are poorly understood. Here we present our current view of how chromatin recognition by DDR factors is achieved at the level of the nucleosome. Emerging evidence suggests that the nucleosome surface, including the nucleosome acidic patch, promotes the binding and activity of several DNA damage factors on chromatin. Thus, in addition to interactions with damaged DNA and histone modifications, nucleosome recognition by DDR factors plays a key role in orchestrating the requisite chromatin response to maintain both genome and epigenome integrity.


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