Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells

Mitochondrial DNA (mtDNA) replication stalling is considered an initial step in the formation of mtDNA deletions that associate with genetic inherited disorders and aging. However, the molecular details of how stalled replication forks lead to mtDNA deletions accumulation are still unclear. Mitochondrial DNA deletion breakpoints preferentially occur at sequence motifs predicted to form G-quadruplexes (G4s), four-stranded nucleic acid structures that can fold in guanine-rich regions. Whether mtDNA G4s form in vivo and their potential implication for mtDNA instability is still under debate. In here, we developed new tools to map G4s in the mtDNA of living cells. We engineered a G4-binding protein targeted to the mitochondrial matrix of a human cell line and established the mtG4-ChIP method, enabling the determination of mtDNA G4s under different cellular conditions. Our results are indicative of transient mtDNA G4 formation in human cells. We demonstrate that mtDNA-specific replication stalling increases formation of G4s, particularly in the major arc. Moreover, elevated levels of G4 block the progression of the mtDNA replication fork and cause mtDNA loss. We conclude that stalling of the mtDNA replisome enhances mtDNA G4 occurrence, and that G4s not resolved in a timely manner can have a negative impact on mtDNA integrity

Global karst springs hydrograph dataset for research and management of the world's fastest-flowing groundwater [Data paper]

Karst aquifers provide drinking water for 10% of the world's population, support agriculture, groundwater-dependent activities, and ecosystems. These aquifers are characterised by complex groundwater-flow systems, hence, they are extremely vulnerable and protecting them requires an in-depth understanding of the systems. Poor data accessibility has limited advances in karst research and realistic representation of karst processes in large-scale hydrological studies. In this study, we present World Karst Spring hydrograph (WoKaS) database, a community-wide effort to improve data accessibility. WoKaS is the first global karst springs discharge database with over 400 spring observations collected from articles, hydrological databases and researchers. The dataset's coverage compares to the global distribution of carbonate rocks with some bias towards the latitudes of more developed countries. WoKaS database will ensure easy access to a large-sample of good quality datasets suitable for a wide range of applications: comparative studies, trend analysis and model evaluation. This database will largely contribute to research advancement in karst hydrology, supports karst groundwater management, and promotes international and interdisciplinary collaborations