Functional conservation and specialization among eukaryotic anti-silencing function 1 histone chaperones.
Chromatin disassembly and reassembly, mediated by histone chaperones such as anti-silencing function 1 (Asf1), are likely to accompany all nuclear processes that occur on the DNA template. In order to gain insight into the functional conservation of Asf1 across eukaryotes, we have replaced the budding yeast Asf1 protein with Drosophila Asf1 (dAsf1) or either of the two human Asf1 (hAsf1a and hAsf1b) counterparts. We found that hAsf1b is best able to rescue the growth defect of Saccharomyces cerevisiae lacking Asf1. Moreover, dAsf1 and hAsf1b but not hAsf1a can replace the role of yeast Asf1 in protecting against replicational stress and activating the PHO5 gene, while only hAsf1a can replace the role of Asf1 in protecting against double-stranded-DNA-damaging agents. Furthermore, it appears that the interaction between Asf1 and the DNA damage checkpoint protein Rad53 is not required for Asf1's role in maintaining genomic integrity. In addition to indicating the functional conservation of the Asf1 proteins across species, these studies suggest distinct roles for the two human Asf1 proteins.
Tamburini
Beth A
BA
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Aurora, Colorado 80010, USA.
Carson
Joshua J
JJ
Adkins
Melissa W
MW
Tyler
Jessica K
JK
D000135:Acid Phosphatase; D000595:Amino Acid Sequence; D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D017124:Conserved Sequence; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D020868:Gene Silencing; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
C109731:ASF1 protein, S cerevisiae; C491641:ASF1A protein, human; C491640:ASF1B protein, human; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D006657:Histones; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C485184:enhanced green fluorescent protein; D001761:Bleomycin; D049452:Green Fluorescent Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D000135:Acid Phosphatase; C488916:PHO5 protein, S cerevisiae