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8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most common marker of oxidative stress and its accumulation within the genome has been associated with major human health issues such as cancer, aging, cardiovascular and neurodegenerative diseases. The characterization of the different genomic sites where 8-oxodG accumulates and the mechanisms underlying its formation are still poorly understood. Using OxiDIP-seq, we recently derived the genome-wide distribution of 8-oxodG in human non-tumorigenic epithelial breast cells (MCF10A). Here, we identify a subset of human promoters that accumulate 8-oxodG under steady-state condition. 8-oxodG nucleotides co-localize with double strand breaks (DSBs) at bidirectional and CG skewed promoters and their density correlate with RNA Polymerase II co-occupancy and transcription. Furthermore, by performing OxiDIP-seq in quiescent (G0) cells, we found a strong reduction of oxidatively-generated damage in the majority of 8-oxodG-positive promoters in the absence of DNA replication. Overall, our results suggest that the accumulation of 8-oxodG at gene promoters occurs through DNA replication-dependent or -independent mechanisms, with a possible contribution to the formation of cancer-associated translocation events.
This article was published in the following journal.
Name: Nucleic acids research
Fragile X mental retardation 1 (FMR1) premutation can cause developmental problems including autism spectrum disorder (ASD), social anxiety, depression, and attention deficit hyperactivity disorder (A...
Understanding the genomic landscape and immune microenvironment features of preinvasive and early-invasive lung adenocarcinoma may provide critical insight and facilitate developing novel strategies f...
Increasing our understanding of how evolutionary processes drive the genomic landscape of variation is fundamental to a better understanding of the genomic consequences of speciation. However, genome-...
Acute myeloid leukemia (AML) is a clinically, morphologically, and genetically heterogeneous disorder. Like many malignancies, the genomic landscape of pediatric AML has been mapped recently through s...
Common fragile sites (CFSs) are breakage-prone genomic loci, and are considered to be hotspots for genomic rearrangements frequently observed in cancers. Understanding the underlying mechanisms for CF...
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This study evaluates the efficacy of multi-odorant enrichment on cognitive skills, olfactory function, and quality of life.
This is a single center study at the UC Davis MIND Institute in patients age 3.5-16 years of age with fragile X syndrome (FXS), funded by a National Fragile X Foundation Grant. It is a con...
Specific loci that show up during KARYOTYPING as a gap (an uncondensed stretch in closer views) on a CHROMATID arm after culturing cells under specific conditions. These sites are associated with an increase in CHROMOSOME FRAGILITY. They are classified as common or rare, and by the specific culture conditions under which they develop. Fragile site loci are named by the letters "FRA" followed by a designation for the specific chromosome, and a letter which refers to which fragile site of that chromosome (e.g. FRAXA refers to fragile site A on the X chromosome. It is a rare, folic acid-sensitive fragile site associated with FRAGILE X SYNDROME.)
A method for analyzing and mapping differences in the copy number of specific genes or other large sequences between two sets of chromosomal DNA. It is used to look for large sequence changes such as deletions, duplications, or amplifications within the genomic DNA of an individual (with a tumor for example) or family members or population or between species.
A RNA-binding protein that is found predominately in the CYTOPLASM. It helps regulate GENETIC TRANSLATION in NEURONS and is absent or under-expressed in FRAGILE X SYNDROME.
An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.
Contiguous large-scale (1000-400,000 basepairs) differences in the genomic DNA between individuals, due to SEQUENCE DELETION; SEQUENCE INSERTION; or SEQUENCE INVERSION.
Adhd Anorexia Depression Dyslexia Mental Health Psychiatry Schizophrenia Stress Mental health, although not being as obvious as physical health, is very important, causing great unhappiness to those affected, causing add...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...