PIF1

PIF1 is a member of the PIF1 family of 5'-to-3' DNA helicases, a group of enzymes in the SF1 superfamily that are conserved from yeast to humans. PIF1 uses ATP hydrolysis to unwind duplex DNA and RNA–DNA hybrids, aiding replication and repair processes at structured or difficult-to-replicate regions such as G-quadruplex DNA and telomeres.

In Saccharomyces cerevisiae, PIF1 contributes to genome stability by promoting replication fork progression and helpfully managing telomere maintenance. It is also localized to mitochondria, where it participates in the maintenance of mitochondrial DNA and overall organellar genome integrity. PIF1 in yeast helps prevent telomere instability by resolving DNA structures that could impede replication.

In humans, PIF1 performs similar roles to support genome stability. It facilitates replication through structured DNA motifs, including G-quadruplexes, at telomeres and other GC-rich regions. Human PIF1 is involved in telomere maintenance and mitochondrial genome maintenance, and it participates in the cellular response to replication stress. Through these functions, PIF1 contributes to appropriate telomere dynamics and the preservation of genome integrity, with implications for cancer biology and aging.

As an evolutionarily conserved helicase, PIF1 is the subject of ongoing research aimed at clarifying its precise mechanisms, regulatory controls, and potential as a therapeutic target in diseases characterized by replication stress, telomere dysfunction, and mitochondrial genome instability.