DNA methyl transferase 1: regulatory mechanisms and implications in health and disease

DNA methylation serves as the principal form of post-replicative epigenetic modification. It is intricately involved in gene regulation and silencing in eukaryotic cells, making significant contributions to cell phenotype. Much of it is mitotically inherited; some is passed on from one filial generation to the next. Establishment and maintenance of DNA methylation patterns in mammals is governed by three catalytically active DNA methyltransferases – DNMT3a, DNMT3b and DNMT1. While the first two are responsible mainly for de novo methylation, DNMT1 maintains the methylation patterns by preferentially catalyzing S-adenosyl methionine-dependant transfer of a methyl group to cytosine at hemimethylated CpG sites generated as a result of semi-conservative DNA replication. DNMT1 contains numerous regulatory domains that fine-tune associated catalytic activities, deregulation of which is observed in several diseases including cancer. In this minireview, we analyze the regulatory mechanisms of various sub-domains of DNMT1 protein and briefly discuss its pathophysiological and pharmacological implications. A better understanding of DNMT1 function and structure will likely reveal new applications in the treatment of associated diseases.     

An overview of the effects of urbanization on the quantity and quality of groundwater in South Asian megacities

One of the challenges facing megacities in South Asian developing countries in their attempts to realize so-called urban rejuvenation is groundwater conditioned by canal seepage and immense sewage loads. To understand the connection between groundwater pollutants and urbanization, numerous studies were reviewed, and data obtained from a variety of national and international organizations were analyzed. In Delhi and Dhaka, urbanization has lowered the groundwater level as a result of severe overextraction, and its dense population makes Delhi particularly vulnerable to groundwater pollution. In the coastal areas of Karachi and Mumbai, such pollution is magnified by the proximity of seawater as well as the increasing populations of these areas. Among the groundwater pollutants associated with urbanization, chlorides and nitrates are the chief anthropogenic toxins; thus, they are examined in this study. This paper concludes with policy recommendations for minimizing the impact of urbanization on groundwater.