A Practical Approach for Targeting Structural Variants Genome-wide in Plasma Cell-free DNA.

Plasma cell-free DNA (cfDNA) is a promising source of gene mutations for cancer detection by liquid biopsy. However, no current tests interrogate chromosomal structural variants (SVs) genome-wide. Here, we report a simple molecular and sequencing workflow called Genome-wide Analysis of Palindrome Formation (GAPF-seq) to probe DNA palindromes, a type of SV that often demarcates gene amplification.

Genome-Wide Analysis of Palindrome Formation with Next-Generation Sequencing (GAPF-Seq) and a Bioinformatics Pipeline for Assessing De Novo Palindromes in Cancer Genomes.

DNA palindromes are a type of chromosomal aberration that appears frequently during tumorigenesis. They are characterized by sequences of nucleotides that are identical to their reverse complements and often arise due to illegitimate repair of DNA double-strand breaks, fusion of telomeres, or stalled replication forks, all of which are common adverse early events in cancer. Here, we describe the protocol for enriching palindromes from genomic DNA sources with low-input DNA amounts and detail a bioinformatics tool for assessing the enrichment and location of de novo palindrome formation from low-coverage whole-genome sequencing data.

TOP1 inhibition induces bifurcated JNK/MYC signaling that dictates cancer cell sensitivity.

Triple-negative breast cancer (TNBC) does not respond to anti-estrogen and anti-HER2 therapies and is commonly treated by chemotherapy. TNBC has a high recurrence rate, particularly within the first 3 years. Thus, there is an urgent clinical need to develop more effective therapies for TNBC.

Quantitative assessment reveals the dominance of duplicated sequences in germline-derived extrachromosomal circular DNA.

Extrachromosomal circular DNA (eccDNA) originates from linear chromosomal DNA in various human tissues under physiological and disease conditions. The genomic origins of eccDNA have largely been investigated using in vitro-amplified DNA. However, in vitro amplification obscures quantitative information by skewing the total population stoichiometry.

Optical and Electron Microscopy for Analysis of Nanomaterials.

Not only is fabrication important for research in materials science, but also materials characterization and analysis. Special microscopes capable of ultra-high magnification are more essential for observing and analyzing nanoparticles than for macro-size particles. Recently, electron microscopy (EM) and scanning probe microscopy (SPM) are commonly used for observing and analyzing nanoparticles.

Luminescent Nanomaterials (I).

From molecular probes, also known as fluorophores (typically emitting a longer wavelength than the absorbing wavelength), to inorganic nanoparticles, various light-emitting materials have been actively studied and developed for various applications in life science owing to their superior imaging and sensing ability. Especially after the breakthrough development of quantum dots (QDs), studies have pursued the development of the optical properties and biological applications of luminescent inorganic nanoparticles such as upconversion nanoparticles (UCNPs), metal nanoclusters, carbon dots, and so on. In this review, we first provide a brief explanation about the theoretical background and traditional concepts of molecular fluorophores.

The fragility of a structurally diverse duplication block triggers recurrent genomic amplification.

The human genome contains hundreds of large, structurally diverse blocks that are insufficiently represented in the reference genome and are thus not amenable to genomic analyses. Structural diversity in the human population suggests that these blocks are unstable in the germline; however, whether or not these blocks are also unstable in the cancer genome remains elusive. Here we report that the 500 kb block called KRTAP_region_1 (KRTAP-1) on 17q12-21 recurrently demarcates the amplicon of the ERBB2 (HER2) oncogene in breast tumors.

NAD+ consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival.

DNA damage signaling is critical for the maintenance of genome integrity and cell fate decision. Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor rapidly activated in a damage dose- and complexity-dependent manner playing a critical role in the initial chromatin organization and DNA repair pathway choice at damage sites. However, our understanding of a cell-wide consequence of its activation in damaged cells is still limited.

Absence of REV3L promotes p53-regulated cancer cell metabolism in cisplatin-treated lung carcinoma cells.

Lung cancer is one of the deadliest cancers in the world because of chemo-resistance to the commonly used cisplatin-based treatments. The use of low fidelity DNA polymerases in the translesional synthesis (TLS) DNA damage response pathway that repairs lesions caused by cisplatin also presents a mutational carcinogenic burden on cells that needs to be regulated by the tumor suppressor protein p53. However, there is much debate over the roles of the reversionless 3-like (REV3L) protein responsible for TLS and p53 in regulating cancer cell metabolism.