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Pif1 helicases are a multifunctional family of DNA helicases that are important for many aspects of genomic stability in the nucleus and mitochondria. Pif1 helicases are conserved from bacteria to humans. Pif1 helicases play multiple roles at the replication fork, including promoting replication through many barriers such as G-quadruplex DNA, the rDNA replication fork barrier, tRNA genes, and R-loops. Pif1 helicases also regulate telomerase and promote replication termination, Okazaki fragment maturation, and break-induced replication. This review highlights many of the roles and regulations of Pif1 at the replication fork that promote cellular health and viability.
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http://dx.doi.org/10.3390/ijms23073736 | DOI Listing |
Blood Adv
September 2025
Institut de Recherches Cliniques de Montreal - IRCM, Montreal, Quebec, Canada.
Acute myeloid leukemia (AML) with rearrangement of the mixed lineage leukemia gene express MLL-AF9 fusion protein, a transcription factor that impairs differentiation and drives expansion of leukemic cells. We report here that the zinc finger protein GFI1 together with the histone methyltransferase LSD1 occupies the promoter and regulates expression of the lncRNA ELDR in the MLL-r AML cell line THP-1. Forced ELDR overexpression enhanced the growth inhibition of an LSD1i/ATRA combination treatment and reduced the capacity of these cells to generate leukemia in xenografts, leading to a longer leukemia-free survival.
View Article and Find Full Text PDFNature
September 2025
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK.
Nuclease-helicase DNA2 is a multifunctional genome caretaker that is essential for cell proliferation in a range of organisms, from yeast to human. Bi-allelic DNA2 mutations that reduce DNA2 concentrations cause a spectrum of primordial dwarfism disorders, including Seckel and Rothmund-Thomson-related syndromes. By contrast, cancer cells frequently express high concentrations of DNA2 (refs.
View Article and Find Full Text PDFSci Adv
August 2025
Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta, 11560 University Avenue, Edmonton T6G 1Z2, Alberta, Canada.
Replication stress (RS) poses a threat to genome stability and drives genomic rearrangements. The homologous recombination (HR) pathway repairs stalled replication forks (RFs) and prevents such instability. Through an E3 ubiquitin ligase screen aimed at identifying regulators of RAD51, we identified macrophage erythroblast attacher (MAEA), a core component of C-terminal to Lish (CTLH) E3 ubiquitin ligase complex, as a regulator of the HR pathway.
View Article and Find Full Text PDFMethods Mol Biol
August 2025
Center for Education in Laboratory Animal Research, Chubu University, Kasugai, Aichi, Japan.
Complex chromosomal rearrangements (CCRs) present significant challenges and opportunities in cancer and congenital disease research. Reproducing these rearrangements experimentally in animal models has been challenging, limiting our insights into their mechanisms and impacts. Recql5 is a critical DNA helicase that participates in replication, transcription, and repair processes.
View Article and Find Full Text PDFInt J Radiat Oncol Biol Phys
August 2025
Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA. Electronic address:
Purpose: Poly ADP ribose polymerase inhibitors (PARPi) are being combined with photon and proton radiotherapy in clinical trials. We sought to investigate mechanisms of PARPi radiosensitization at varying linear energy transfer (LET) levels after observing an extreme normal tissue response in an 18-year-old with high grade glioma without a germline alteration predictive of heightened radiosensitivity treated with veliparib and proton therapy.
Experimental Design: BRCA1/2 wild-type non-cancerous and cancerous cells were treated with PARPi plus photons or protons at the entrance (ENT, dose-averaged LET [LETd] 2.