Random Records

Note: Transcription-Coupled DNA Double-Strand Break Repair: Active Genes Need Special Care (doi: 10.1371/journal.pgen.1006895) Specific loci on eukaryotic chromosomes are inherently susceptible to breakage. Transcriptionally active loci are particularly fragile and that a specific DNA damage response is activated and dedicated to their repair. Review on – crosstalk between transcription and double-strand break repair, from intrinsic fragility of genes to the mechanisms that restore the integrity of damaged transcription units. DNA double helix is irregular: it can form non-canonical structures such as R-loops (three stranded structures composed of RNA:DNA hybrids and single-stranded DNA), hairpins, G-quadruplex (G4), and underwound or over-twisted DNA helices that are further translated into negative and positive supercoiling. The transcription, replication, and repair machineries must cope with this great variety of secondary and tertiary structures if they are to accurat

To remind myself a bit Nonsense mutation -- causing the stop codon Missense mutation/Nonsynonymous mutation -- causing the amino acids change Silent mutation/Synonymous mutation-- causing no change in amino acid Neutral mutation -- causing the amino acid change but the protein function does not change Frameshift mutation -- causing the reading frame changed

Note for: DNA double-strand break repair in a cellular context (doi: 10.1016/j.clon.2014.02.004) Tumour cells not only gain unlimited proliferative capacity, but the ability to adapt to a constantly changing microenvironment. DDR is modified to serve the cancerous phenotype, and if we understand the reasons behind we can get the right target to against the cancer. Non-homologous end-joining (NHEJ) represents the major DNA double-strand break (DSB) repair pathway in mammalian cells. DNA-PKcs undergoes autophosphorylation at clustered sites. DNA-PKcs undergoes autophosphorylation at clustered sites. End-processing can involve the Artemis nuclease, polynucleotide kinase 3' phosphatase and polymerases, including pol-lamda or pol-mu. Whereas NHEJ has beauty in its simplicity, homologous recombination’s elegance lies in its complexity and its exploitation of an undamaged homologous template to restore any lost sequence information. One such process is alternative NHEJ

Note for: ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response doi: 10.1016/j.molcel.2017.05.015 Freaking complicated and so many gaps in the research as well as the available tool to elaborate precise mechanism. In general, a cell’s DNA damage response (DDR) involves DNA lesion recognition, followed by initiation of a cellular signaling cascade to promote DNA repair, which can be aided by a pause in cell-cycle progression (checkpoint activation). In concert with such events, cells mediate other responses, including modulation of chromatin structure and transcription, both at sites of DNA damage and more globally. DNA damage permanently exit the cell cycle (senescence) or undergo programmed cell death (apoptosis), presumably to mitigate the propagation of potentially mutated cells leading to cancer or other age-related pathologies. DNA lesions also serve as intermediates in certain biological processes, such as DNA demethylation, meiotic recombina

As far as I have heard and read; 1.Cancer stem cell Cancer behaves like a stem cell. It can divide indefinitely and can differentiate into the other cell type. 2.Field cancerization Cancer occurs when the normal cell has been chronically exposed to the carcinogens. Then the molecular genetics have been changed along the way until the injured cell loses control in cell division. 3.Mutator phenotype It relies on the fact that the machinery of DNA replication has been less effective over time and causing the error in replication, which leads to DNA mutations. Besides, DNA repair also contributes to the mutator phenotype. Defective in DNA repair causes the accumulated DNA mutations. All of these factors, in turn, change the cellular division regulation and thereby leading to carcinogenesis. What else?

Note for: Computer-Aided Drug Design of Bioactive Natural Products (doi: 10.2174/1568026615666150506151101 ) The associated data mining tools are useful for creating databases, and molecular docking is capable of identifying potential targets by docking drugs to large libraries of proteins. The process of hit identification can be performed using high throughput screening (HTS) and virtual screening. Virtual screening is an effective means of searching for potential compounds by using computational approaches. One widely used computational method in this process is molecular docking. Active compounds with good binding affinity to the target, represented by a docking score. Privileged structures are defined as molecular substructures that are capable of binding to a diverse array of receptors, and the modification of these substructures can provide an alternative approach to the discovery of novel receptor agonists and antagonists. Diverse types of privileged st