title: RECQL5 has unique strand annealing properties relative to the other human RecQ helicase proteins.
abstract: The RecQ helicases play important roles in genome maintenance and DNA metabolism (replication, recombination, repair, and transcription). Five different homologs are present in humans, three of which are implicated in accelerated aging genetic disorders: Rothmund Thomson (RECQL4), Werner (WRN), and Bloom (BLM) syndromes. While the DNA helicase activities of the 5 human RecQ helicases have been extensively characterized, much less is known about their DNA double strand annealing activities. Strand annealing is an important integral enzymatic activity in DNA metabolism, including DNA repair. Here, we have characterized the strand annealing activities of all five human RecQ helicase proteins and compared them. Interestingly, the relative strand annealing activities of the five RecQ proteins are not directly (inversely) related to their helicase activities. RECQL5 possesses relatively strong annealing activity on long or small duplexed substrates compared to the other RecQs. Additionally, the strand annealing activity of RECQL5 is not inhibited by the presence of ATP, unlike the other RecQs. We also show that RECQL5 efficiently catalyzes annealing of RNA to DNA in vitro in the presence or absence of ATP, revealing a possible new function for RECQL5. Additionally, we investigate how different known RecQ interacting proteins, RPA, Ku, FEN1 and RAD51, regulate their strand annealing activity. Collectively, we find that the human RecQ proteins possess differential DNA double strand annealing activities and we speculate on their individual roles in DNA repair. This insight is important in view of the many cellular DNA metabolic actions of the RecQ proteins and elucidates their unique functions in the cell.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program (NIA IRP), Biomedical Research Center, Baltimore, MD 21224, USA.
authors.forename: Prabhat
authors.initials: P
authors.lastname: Khadka
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program (NIA IRP), Biomedical Research Center, Baltimore, MD 21224, USA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Croteau
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program (NIA IRP), Biomedical Research Center, Baltimore, MD 21224, USA. Electronic address: vbohr@nih.gov.
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D000255:Adenosine Triphosphate; D034961:Antigens, Nuclear / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D045585:Flap Endonucleases / Q000378:metabolism; D006801:Humans; D000072200:Ku Autoantigen; D051135:Rad51 Recombinase / Q000378:metabolism; D053484:RecQ Helicases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C506732:RECQL5 protein, human; D000255:Adenosine Triphosphate; D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D045585:Flap Endonucleases; C468317:FEN1 protein, human; D053484:RecQ Helicases; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen
keywords: Aging; DNA repair; DNA–DNA hybrid; RNA–DNA hybrid; RecQ helicase; Strand annealing