Biology subjects

Abrantes, K.

Publications and source records attributed to Abrantes, K..

3 recordsLinked to original sources

bioRxiv2025

A non-catalytic role for RFC in PCNA-mediated processive DNA synthesis

The ring-shaped sliding clamp PCNA enables DNA polymerases to perform processive DNA synthesis during replication and repair. The loading of PCNA onto DNA is catalyzed by the ATPase clamp loader RFC. Using a single-molecule platform to visualize the dynamic interplay between PCNA and RFC on DNA, we unexpectedly discovered that RFC continues to associate with PCNA after loading, contrary to the conventional view. Functionally, this clamp-loader/clamp complex is required for processive DNA synthesis by polymerase {delta} (Pol{delta}), as the PCNA-Pol{delta} assembly is inherently unstable. This architectural role of RFC is dependent on the BRCT domain of Rfc1, and mutation of its DNA-binding residues causes sensitivity to DNA damage in vivo. We further showed the FEN1 flap endonuclease can also stabilize the PCNA-Pol{delta} interaction and mediate robust synthesis. Overall, our work revealed that, beyond their canonical enzymatic functions, PCNA-binding proteins harbor non-catalytic functions essential for DNA replication and genome maintenance.

biophysics↗

bioRxiv2024

The global fish and invertebrate abundance value of mangroves

Mangroves are a critical coastal habitat that provides a suite of ecosystem services and supports livelihoods. We undertake the first global analysis to estimate density and abundance of 37 commercially important fish and invertebrates that are known to extensively use mangroves. Geomorphic mangrove type, sea surface salinity and temperature, and length of mangrove forest edge were important in predicting the density of commercial fish and invertebrates, with deltaic systems supporting the highest densities. The model predicted high densities throughout parts of southeast Asia, the northern coast of South America, the Red Sea, and the Caribbean and Central America. Application of our model onto the global mangrove extent, estimates that mangroves support the annual abundance of nearly 800 billion young-of-year fish and invertebrates contained in our model. Our results confirm the critical role of mangroves globally in supporting fish and fisheries, and further builds the case for their conservation and restoration.

ecology↗

bioRxiv2022

Restricting α-Synuclein Transport into Mitochondria by Inhibition of α-Synuclein-VDAC Complexation as a Potential Therapeutic Target for Parkinson's Disease Treatment

Involvement of alpha-synuclein (Syn) in Parkinsons disease (PD) is complicated and difficult to trace on cellular and molecular levels. Recently we established that Syn can regulate mitochondrial function by voltage-activated complexation with the Voltage-Dependent Anion Channel (VDAC) of the outer mitochondrial membrane. When complexed with Syn, the VDAC pore is partially blocked, reducing the transport of ATP/ADP and other metabolites. Further, Syn can translocate into the mitochondria through VDAC, where it interferes with mitochondrial respiration. Recruitment of Syn to the VDAC-containing lipid membrane appears to be a crucial prerequisite for both the blockage and translocation processes. Here we report an inhibitory effect of HK2p, a small membrane-binding peptide from the mitochondria-targeting N-terminus of hexokinase 2, on the Syn membrane binding, and hence on Syn complex formation with VDAC and translocation through it. In electrophysiology experiments, addition of HK2p at micromolar concentrations to the same side of the membrane as Syn results in dramatic reduction of the frequency of blockage events in a concentration-dependent manner, reporting on complexation inhibition. Using two complementary methods of measuring protein-membrane binding, bilayer overtone analysis and fluorescence correlation spectroscopy, we found that HK2p induces detachment of Syn from lipid membranes. Experiments with live HeLa cells using proximity ligation assay confirmed that HK2p impedes Syn entry into mitochondria. Our results demonstrate that it is possible to regulate Syn-VDAC complexation by a rationally designed peptide, thus suggesting new avenues in the search for peptide therapeutics to alleviate Syn mitochondrial toxicity in PD and other synucleinopathies.

biophysics↗