The Gam protein of bacteriophage Mu is an orthologue of eukaryotic Ku.
Mu bacteriophage inserts its DNA into the genome of host bacteria and is used as a model for DNA transposition events in other systems. The eukaryotic Ku protein has key roles in DNA repair and in certain transposition events. Here we show that the Gam protein of phage Mu is conserved in bacteria, has sequence homology with both subunits of Ku, and has the potential to adopt a similar architecture to the core DNA-binding region of Ku. Through biochemical studies, we demonstrate that Gam and the related protein of Haemophilus influenzae display DNA binding characteristics remarkably similar to those of human Ku. In addition, we show that Gam can interfere with Ty1 retrotransposition in Saccharomyces cerevisiae. These data reveal structural and functional parallels between bacteriophage Gam and eukaryotic Ku and suggest that their functions have been evolutionarily conserved.
d'Adda di Fagagna
Fabrizio
F
The Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, UK.
Weller
Geoffrey R
GR
Doherty
Aidan J
AJ
Jackson
Stephen P
SP
D000595:Amino Acid Sequence; D034961:Antigens, Nuclear / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry; D010583:Bacteriophage mu / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000737:chemistry*; D019281:Dimerization; D005057:Eukaryotic Cells / Q000378:metabolism; D019143:Evolution, Molecular; D006193:Haemophilus influenzae / Q000737:chemistry / Q000235:genetics; D006801:Humans; D000072200:Ku Autoantigen; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018626:Retroelements / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014764:Viral Proteins / Q000737:chemistry*
D034961:Antigens, Nuclear; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D018626:Retroelements; D014764:Viral Proteins; C065410:gam protein, Coliphage; D004247:DNA; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen