Meah, R. | Search bioRxiv

bioRxiv2025

Single-molecule analysis of PARP1-G-quadruplex interaction

The human genome contains numerous repetitive nucleotide sequences that display a propensity to fold into non-canonical DNA structures including G-quadruplexes (G4s). G4s have both positive and negative impacts on various aspects of nucleic acid metabolism including DNA replication, DNA repair and RNA transcription. Poly (ADP-ribose) polymerase (PARP1), an important anticancer drug target, has been recently shown to bind a subset of G4s, and to undergo auto-PARylation. The mechanism of this interaction, however, is poorly understood. Utilizing Mass Photometry (MP) and single-molecule total internal reflection fluorescence microscopy (smTIRFM), we demonstrate that PARP1 dynamically interacts with G4s with a 1:1 stoichiometry. Interaction of a single PARP1 molecule with nicked DNA or DNA containing G4 and a primer-template junction is sufficient to activate robust auto-PARylation resulting in the addition of poly (ADP-ribose) chains with molecular weight of several hundred kDa. Pharmacological PARP inhibitors EB-47, Olaparib and Veliparib differently affect PARP1 retention on G4-containing DNA compared to nicked DNA.

biophysics↗

bioRxiv2018

Spatial and ontogenetic variation in susceptibility to polarotactic ecological traps

Ecological traps occur when environmental cues become unreliable, causing an evolutionary mismatch between features of the environment and expected outcome that leads to suboptimal behavioural responses and, ultimately, reduced fitness. Ecological traps arise due to anthropogenic disturbance in the environment introducing novel elements that mimic those environmental cues. Therefore, ecological traps represent a strong selective pressure in areas where anthropogenic changes are frequent, such as cities. However, given the exposure to these traps over generations, localised adaptations to ecological traps might be expected in urban populations. Dragonflies and damselflies (Odonata) are one of the many taxa vulnerable to ecological traps: odonates use horizontally polarised light as a cue of suitable water bodies, although some artificial surfaces also reflect horizontally polarised light strongly, thus misleading odonates to oviposit preferentially on these unsuitable surfaces rather than in water. Here, we compare the behavioural response to horizontally polarised light between urban and rural populations of the odonate Ischnura elegans to test the potential for localised adaptations to ecological traps. Laboratory choice experiments were performed using field-caught adults from urban and rural areas, and individuals reared in controlled conditions to account for environmental variation and exposure to polarised light. We also studied the association between ontogeny and polarotaxis that has been suggested - but not empirically tested - by other studies. The results showed that field-caught rural individuals had a significantly stronger preference for horizontally polarised light compared to urban individuals, suggesting there is strong selection against polarotaxis in urban areas. However, individuals reared in controlled conditions showed no difference between urban and rural populations, suggesting that there has not yet been adaptation in urban odonates. Instead, adults developed a strong preference for horizontally polarised light with increasing age, showing that mature adults are more prone to ecological traps. Possible mechanisms driving this response are discussed.

evolutionary biology↗