Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress.
The recently characterized enzyme NEIL2 (Nei-like-2), one of the four oxidized base-specific DNA glycosylases (OGG1, NTH1, NEIL1, and NEIL2) in mammalian cells, has poor base excision activity from duplex DNA. To test the possibility that one or more proteins modulate its activity in vivo, we performed mass spectrometric analysis of the NEIL2 immunocomplex and identified Y box-binding (YB-1) protein as a stably interacting partner of NEIL2. We show here that YB-1 not only interacts physically with NEIL2, but it also cooperates functionally by stimulating its base excision activity by 7-fold. Moreover, YB-1 interacts with the other NEIL2-associated BER proteins, namely, DNA ligase III alpha and DNA polymerase beta and thus could form a large multiprotein complex. YB-1, normally present in the cytoplasm, translocates to the nucleus during UVA-induced oxidative stress, concomitant with its increased association with and activation of NEIL2. NEIL2-initiated base excision activity is significantly reduced in YB-1-depleted cells. YB-1 thus appears to have a novel regulatory role in NEIL2-mediated repair under oxidative stress.
Das
Soumita
S
Sealy Center for Molecular Medicine and Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555.
Chattopadhyay
Ranajoy
R
Sealy Center for Molecular Medicine and Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555.
Bhakat
Kishor K
KK
Sealy Center for Molecular Medicine and Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555.
Boldogh
Istvan
I
Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555.
Kohno
Kimitoshi
K
Department of Molecular Biology, University of Occupational and Environmental Health School of Medicine, Iseigaoka, Kitakyushu, Japan.
Prasad
Rajendra
R
Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Wilson
Samuel H
SH
Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Hazra
Tapas K
TK
Sealy Center for Molecular Medicine and Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555. Electronic address: tkhazra@utmb.edu.
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism*; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism; D019951:DNA Polymerase beta / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology* / Q000528:radiation effects; D000075223:Poly-ADP-Ribose Binding Proteins; D014466:Ultraviolet Rays; D029867:Xenopus Proteins; D051840:Y-Box-Binding Protein 1
D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D019951:DNA Polymerase beta; D045647:DNA Glycosylases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C473642:NEIL2 protein, human; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human