Genetic regulatory mechanisms in the synthesis ..

All rights reserved GENETIC REGULATORY MECHANISMS IN THE FUNGP By SAMSON R.

Genetic regulatory mechanisms in the synthesis of proteins

A summary of bacterial protein toxins and their activities is givenin Tables 4. Details of the mechanisms of action of these toxins andtheirinvolvementin the pathogenesis of disease is discussed in chapters with thespecificbacterial pathogens.

Genetic Regulatory Mechanisms in the Fungi - …

Mechanisms of Protein Synthesis by the Ribosome

Telomerase is suppressed in the majority of somatic cells leading to the continuing telomere attrition, which leads to irreversible cell-cycle arrest known as replicative cell senescence. It has been demonstrated that primary human fibroblasts that have lost the ability to senesce, display telomere shortening and eventually enter a crisis stage that culminates in chromosome fusion, aneuploidy and cell death (Counter et al., 1992). It has been proposed that it is therefore important for cancer cells to regain the ability to maintain telomeres, in order to avoid senescence and extensive chromosome fusion during crisis (Counter et al., 1992; Harley, 1995). In fact it has been shown that about 85-90% of human cancers have reactivated telomerase and are able to maintain telomere length (Jefford and Irminger-Finger, 2006). Interestingly cancer cells that are deficient for telomerase activity are able to maintain telomere length via a mechanism known as alternative lengthening of telomeres or ALT. It has been suggested that the ALT mechanism makes use of DNA repair pathways and recombination to maintain telomere length (Reddel, 2003). Thus, whichever mechanism employed by the cell, it appears that maintaining telomere length is critical for tumourigenesis and cellular immortalization (Jefford and Irminger-Finger, 2006). Telomere maintenance is also required for chromosomal instability. Given that cancer cells inevitably display properties of telomere maintenance and genetic instability, it has been proposed that telomere loss could be either a cause or a consequence of genetic instability (Jefford and Irminger-Finger, 2006), or perhaps be involved in both.

Mechanisms of Protein Synthesis by ..

The regulatory mechanisms in branched-chain amino acid synthesis were compared between 2-thiazolealanine (2-TA) resistant L-leucine and L-valine producing mutants and the 2-TA sensitive original strains of 2256.
In the original strains, sensitive to 2-TA, α-isopropylmalate (IPM) synthetase, the initial enzyme specific for L-leucine synthesis, is sensitive to feedback inhibition and to repression by L-leucine, and α-acetohydroxy acid (AHA) synthetase, the common initial enzyme for synthesis of L-isoleucine, L-valine as well as L-leucine, is sensitive to feedback inhibition by each one of these amino acids, and to repression by them all. In strain No. 218, a typical L-leucine producer resistant to 2-TA, IPM synthetase was found to be markedly desensitized and derepressed, and AHA synthetase remained unaltered. On the contrary, in strain No. 333, L-valine producer resistant to 2-TA, AHA synthetase was found to be desensitized and partially derepressed, and IPM synthetase remained unaltered.
The genetic alteration of these regulatory mechanisms was discussed in connection with the accumulation pattern of amino acids.

Genetic Regulatory Mechanisms in the Fungi - DeepDyve


Genetic Regulatory Mechanisms in the Fungi

It is the interplay between histone acteylases (HATs) and histone deacetylates (HDACs) that determine the precise balance of acetylation within the nucleus. Abnormal HDAC activity has been commonly observed in (Espino et al., 2005). Studies done in these cancers have shown that fusion proteins such as and can recruit HDACs, which in turn lead to aberrant transcriptional repression that halts differentiation (de Ruijter et al., 2003; Hong et al., 1997). It has been proposed that a dynamic relationship exists between histone modifications, chromatin structure and DNA methylation (Szyf et al., 2004; Ting et al., 2004). For example it has been shown that histone acetylation and gene activation, results in DNA demethylation (Szyf et al., 2004), while the opposite situation where low steady state level of histone acetylation and methylation, results in the recruitment of DNMT1 and DNA methylation of regulatory regions (Espino et al., 2005). Thus, it is mechanistically possible that skewed regulation of this inter-relationship could lead to genetic instability.

Genetic Regulatory Mechanisms in the Synthesis of ..

CpG islands commonly occur in the promoter regions, thus hypermethylation of this region has been shown to silence gene expression (Bird, 2002). This was first identified in the retinoblastoma protein () followed by promoter hypermethylation of several other tumour suppressor and cell-cycle regulatory genes (Greger et al., 1989). It is believed that hypermethylation too is an early event that may precede the neoplastic process (Momparler, 2003; Nephew and Huang, 2003). A prime example of the role of hypermethylation in contributing to genetic instability is hMLH1 inactivation, where promoter hypermethylation is thought to be primarily responsible for approximately 15% of sporadic colorectal cancers associated with microsatellite instability (Kane et al., 1997; Herman et al., 1998). In a study by Costello et al. (Lander et al., 2001), 1184 unselected CpG islands were screened in 98 primary human tumours using restriction landmark genomic scanning (RLGS). This study found that on average about 600 CpG islands were aberrantly methylated in tumours, indicating the potentially vast number of genes likely to be aberrantly expressed due to this mechanism.

GENETIC REGULATION OF DEVELOPMENT AND AFLATOXIN SYNTHESIS IN ..

One mechanism that can bring about chromosomal instability (CIN) is telomere loss. Although CIN is not addressed in detail in this paper, the role of is briefly summarized to highlight the important role it may play in carcinogenesis and the implications it may have in the field of genetic instability.