title: Borrowing nuclear DNA helicases to protect mitochondrial DNA.
abstract: In normal cells, mitochondria are the primary organelles that generate energy, which is critical for cellular metabolism. Mitochondrial dysfunction, caused by mitochondrial DNA (mtDNA) mutations or an abnormal mtDNA copy number, is linked to a range of human diseases, including Alzheimer's disease, premature aging‎ and cancer. mtDNA resides in the mitochondrial lumen, and its duplication requires the mtDNA replicative helicase, Twinkle. In addition to Twinkle, many DNA helicases, which are encoded by the nuclear genome and are crucial for nuclear genome integrity, are transported into the mitochondrion to also function in mtDNA replication and repair. To date, these helicases include RecQ-like helicase 4 (RECQ4), petite integration frequency 1 (PIF1), DNA replication helicase/nuclease 2 (DNA2) and suppressor of var1 3-like protein 1 (SUV3). Although the nuclear functions of some of these DNA helicases have been extensively studied, the regulation of their mitochondrial transport and the mechanisms by which they contribute to mtDNA synthesis and maintenance remain largely unknown. In this review, we attempt to summarize recent research progress on the role of mammalian DNA helicases in mitochondrial genome maintenance and the effects on mitochondria-associated diseases.
authors.affiliation: Department of Radiation Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010-3000, USA. lding@coh.org.
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Radiation Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010-3000, USA. yiliu@coh.org.
authors.forename: Yilun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological
chemical_list: D004272:DNA, Mitochondrial; D004265:DNA Helicases
keywords: DNA repair; DNA replication; DNA2; PIF1; RECQ4; SUV3; Twinkle; mitochondrial DNA