Biology subjects

Aslan, E.

Publications and source records attributed to Aslan, E..

3 recordsLinked to original sources

bioRxiv2026

A PIWI protein-dependent DNA N6-adenine methylation pathway in Oxytricha protects genomic sequences from deletion

The ciliate Oxytricha undergoes massive genome rearrangements during development to produce a functional nucleus from an encrypted zygotic genome. PIWI-interacting small RNAs protect DNA regions against deletion, but how that protective mark is established has been a mystery. Recently our lab discovered MTA1, a methyltransferase that catalyzes DNA N6-adenine (6mA) methylation. Both MTA1 and the Oxytricha Piwi protein, Otiwi1, are required for development, and Otiwi1 mutation eliminates 6mA signal. To examine the role of 6mA, we analyzed its genome-wide distribution across development in wild-type and MTA1 mutant backcrossed cells. We find specific and abundant enrichment on retained sequences, suggesting a protective role for this epigenetic mark. Furthermore, programmed retention of a DNA region that is normally deleted leads to accumulation of new 6mA marks on the ectopically retained DNA sequence. Together, these results suggest that piRNA-guided 6mA DNA methylation leads to protection of DNA sequences against deletion during nuclear differentiation. HighlightsO_LIDNA N6-methyladenine accumulates on retained DNA regions during Oxytricha development. C_LIO_LImta1 mutant backcrosses have disrupted DNA methylation and a developmental delay. C_LIO_LIDNA N6-adenine methylation during genome rearrangement requires the presence of Otiwi1. C_LIO_LIProgrammed retention of a germline-limited region leads to developmental methylation. C_LI

molecular biology↗

bioRxiv2025

Relaxed DNA substrate specificity of transposases involved in programmed genome rearrangement

During post-zygotic development, the ciliate Oxytricha trifallax undergoes massive programmed genome rearrangement that involves over 225,000 DNA cleavage and joining events. An Oxytricha family of Tc1/mariner transposons, known as Telomere-Bearing Elements (TBEs), encodes a transposase that has been implicated in rearrangement, but its high copy number (>34,000 paralogs) has precluded genetic strategies to investigate its DNA recognition properties directly in Oxytricha. Here, we developed a heterologous strategy to assay TBE transposase expression and activity in E. coli, revealing highly promiscuous DNA cleavage properties. Systematic ChIP-seq experiments allowed us to define the DNA binding specificities of multiple distinct transposase subfamilies, which exhibited a binding and cleavage preference for short, degenerate sequence motifs that resemble features present within the TBE transposon ends. The relaxed sequence preference is striking for autonomous transposases, which typically recognize their end sequences with strict specificity to avoid compromising host fitness. Finally, we developed a custom antibody to investigate TBE transposases in their native environment and found that they precisely localize to the developing nucleus exclusively during the rearrangement process. Collectively, this work establishes a robust heterologous workflow for the biochemical investigation of enzymes that have been repurposed for large-scale genome rearrangements.

molecular biology↗

bioRxiv2024

Impact of juglone on oral carcinogenesis induced by 4-nitroquinoline-1-oxide (4NQO) in rat model

In this study, the potential effects of juglone, also known as PIN1 inhibitor, on oral cancer and carcinogenesis were investigated at the molecular level. 4-Nitroquinoline N-oxide (4-NQO) was used to create an oral cancer model on animals. Wistar rats were divided into five groups; Control, NQO, Juglone, NQO+J, and NQO+J*. The tongue tissues of the rats were isolated after the experiment, morphological changes were investigated by histological examinations, and the molecular apoptotic process was investigated by rt-qPCR and Western blot. Histological results indicate that tumors are formed in the tongue tissue with 4-NQO, and juglone treatment largely corrects the epithelial changes that developed with 4-NQO. It has been determined that apoptotic factors p53, Bax, and caspases are induced by the effect of juglone, while antiapoptotic factors such as Bcl-2 are suppressed. However, it was observed that the positive effects were more pronounced in rats given juglone together with 4-NQO. The use of PIN1 inhibitors such as juglone in place of existing therapeutic approaches might be a promising and novel approach to the preservation and treatment of oral cancer and carcinogenesis. However, further research is required to investigate the practical application of such inhibitors.

pharmacology and toxicology↗