Chromosomal modifications

More valuable information on nucleic acids has been obtained from pyrolysis data when it was possible to evaluate the nature and abundance of the purine/pyrimidine bases. The information on these bases is important for monitoring in vitro DNA synthesis [5,6], for the evaluation of chromosome modifications [7], and for the study of complex formation of DNA with cisplatin [11,12]. As indicated previously, the DIP technique was reported to be more useful for detecting the base component of the nucleic acid. However, some information on the bases can be obtained also by Curie point Py-MS, as it can be seen from the spectrum of NADPH (nicotinamide adenine dinucleotide phosphate) shown in Figure 13.2.3. The spectrum was obtained in similar conditions as spectra for DNA and RNA shown previously [8]. 

The interaction of DNA with M + ions produces modifications in SAR, with undesirable biological effects. Consecutive effects of the interactions undergone by some metals with living matter (Woollam 1972, Kazantsis et al 1979) attest to the involvement of DNA, and lead to appearance of chromosomal modifications as well as mutagenic, oncogenic, and teratogenic effects... 

Almost all of the proposed tests have to do with changes at the DNA or chromosome level. These DNA alterations (mutations, covalent adduct formation, etc.) or chromosomal modifications (sister chromatid exchange, micronucleus test, etc.) are proposed to be predictive of carcinogens. It is not claimed that they have any predictive value for non-neoplastic diseases. 

Chromosomal Modification with Transiently Employed Selection Markers 238... 

Fig. 3. Chromosomal modifications. Targeting of the two loxP sites some distance apart, either in cis (A) or in trans, in the same (B), or different chromosomes (C) can give rise to various chromosomal modifications.

Histone phosphorylation is a common posttranslational modification fond in histones, primarily on the N-terminal tails. Phosphorylation sites include serine and threonine residues, tyrosine phosphorylation has not been observed so far. Some phosphorylation events occur locally whereas others occur globally throughout all chromosomes during specific events like mitosis. Histone phosphorylation is catalyzed by kinases. Removal of the phosphoryl groups is catalyzed by phosphatases. 

Restriction/modification Degradation of DNA Chromosome-associated proteins Other... 

In addition to the role for the nucleosome-nucleosome interactions, the histone tails are known as the region that undergoes post-transcriptional modifications, such as acetylation, phosphorylation, and methylation (Fig. Ic) (Peterson and Laniel, 2004). These modifications trigger the formation of euchromatin (acetylation), heterochromatin (methylation), or metaphase chromosome (phosphorylation). The details of these modifications will be described in chapters 8-11. 

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