title: Human Rev1 polymerase disrupts G-quadruplex DNA.
abstract: The Y-family DNA polymerase Rev1 is required for successful replication of G-quadruplex DNA (G4 DNA) in higher eukaryotes. Here we show that human Rev1 (hRev1) disrupts G4 DNA structures and prevents refolding in vitro. Nucleotidyl transfer by hRev1 is not necessary for mechanical unfolding to occur. hRev1 binds G4 DNA substrates with Kd,DNA values that are 4-15-fold lower than those of non-G4 DNA substrates. The pre-steady-state rate constant of deoxycytidine monophosphate (dCMP) insertion opposite the first tetrad-guanine by hRev1 is ∼56% as fast as that observed for non-G4 DNA substrates. Thus, hRev1 can promote fork progression by either dislodging tetrad guanines to unfold the G4 DNA, which could assist in extension by other DNA polymerases, or hRev1 can prevent refolding of G4 DNA structures. The hRev1 mechanism of action against G-quadruplexes helps explain why replication progress is impeded at G4 DNA sites in Rev1-deficient cells and illustrates another unique feature of this enzyme with important implications for genome maintenance.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA and Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Sarah
authors.initials: S
authors.lastname: Eddy
authors.forename: Amit
authors.initials: A
authors.lastname: Ketkar
authors.forename: Maroof K
authors.initials: MK
authors.lastname: Zafar
authors.forename: Leena
authors.initials: L
authors.lastname: Maddukuri
authors.forename: Jeong-Yun
authors.initials: JY
authors.lastname: Choi
authors.forename: Robert L
authors.initials: RL
authors.lastname: Eoff
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D003843:Deoxycytidine Monophosphate / Q000378:metabolism; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism*; D000099270:Y-Family DNA Polymerases
chemical_list: D004247:DNA; D003843:Deoxycytidine Monophosphate; D006147:Guanine; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases