bioRxiv Science⌕ Search

Biology subjects

Latimer, J. J.

Publications and source records attributed to Latimer, J. J..

2 recordsLinked to original sources

Greater Expression of DNA Repair Pathways in Sharks vs. Rays/Skates Based on Transcriptomic Analyses

Elasmobranchs are an understudied taxon of cartilaginous fishes. DNA repair studies have been performed in very few elasmobranchs. Because DNA repair maintains the integrity of the genetic code, it is important for the survival of elasmobranchs in increasingly polluted oceans. Oil spills, for example, have been shown to cause DNA adducts in marine animals. We hypothesized that four elasmobranch species would show differential DNA repair expression. Dermal tissue was harvested from nurse sharks (Ginglymostoma cirratum), spiny dogfish (also considered to be sharks) (Squalus acanthias), yellow stingrays (Urobatis jamaicensis), little skates (Leucoraja erinacea), and RNA was isolated. RNA sequencing was performed using the holocephalan Australian ghostshark (Callorhincus milii) reference genome. ANOVA KEGG pathway analysis revealed that RNA from the sharks manifested significantly higher expression than those of rays/skates in 4/5 major DNA repair pathways (Base Excision, Nucleotide Excision, Mismatch Repair, and Homologous Recombination). Each of the four pathways of DNA repair manifested differential expression of pathway-specific genes (mpg, polL, parp4, polD2, xpa, gtf2h3, gtf2h5, ercc8, ercc4, cul4b, rad51D, rad51C, blm, ssbp1, top3a, rad51, xrcc3, mre11a, brip1, rad54b, etc.). One gene, polD2, was consistently elevated in the sharks vs. rays/skates in all four pathways. A subunit of polD, has been proposed to contribute to the spreading and amplification of hypermutations in sharks by generating higher diversity of the T cell receptor repertoire. With increased expression of four major DNA repair pathways, sharks may be more successful than rays/skates in remediating DNA damage and surviving the genotoxic effects of increasingly polluted oceans and possibly eluding cancer.

molecular biology↗

Cancer-Specific Alterations in Nuclear Matrix Proteins Determined by Multi-omics Analyses of Ductal Carcinoma in Situ

Breast cancer (BC) is the most common cancer affecting women in the United States. Ductal carcinoma in situ (DCIS) is the earliest identifiable pre-invasive BC lesion. Estimates show that 14 to 50% of DCIS cases progress to invasive BC. Our objective was to identify nuclear matrix proteins (NMP) with specifically altered expression in DCIS and later stages of BC compared to non-diseased breast reduction mammoplasty and a contralateral breast explant using mass spectrometry and RNA sequencing to accurately identify aggressive DCIS. Sixty NMPs were significantly differentially expressed between the DCIS and non-diseased breast epithelium in an isogenic contralateral pair of patient-derived extended explants. Ten of the sixty showed significant mRNA expression level differences that matched the protein expression. These 10 proteins were similarly expressed in non-diseased breast reduction cells. Three NMPs (RPL7A, RPL11, RPL31) were significantly upregulated in DCIS and all other BC stages compared to the matching contralateral breast culture and an unrelated non-diseased breast reduction culture. RNA sequencing analyses showed that these three genes were upregulated increasingly with BC progression. Finally, we identified three NMPs (AHNAK, CDC37 and DNAJB1) that were significantly downregulated in DCIS and all other BC stages compared to the isogenically matched contralateral culture and the non-diseased breast reduction culture using both proteomics and RNA sequencing techniques.

cancer biology↗