Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress

Soumita Das, Ranajoy Chattopadhyay, Kishor K. Bhakat, Istvan Boldogh, Kimitoshi Kohno, Rajendra Prasad, Samuel H. Wilson, Tapas Hazra

Research output: Contribution to journalArticle

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Abstract

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 IIIα and DNA polymerase β 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.

Original languageEnglish (US)
Pages (from-to)28474-28484
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number39
DOIs
StatePublished - Sep 28 2007

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Oxidative stress
DNA Repair
Y-Box-Binding Protein 1
Oxidative Stress
Repair
DNA Polymerase III
DNA Glycosylases
DNA Ligases
Multiprotein Complexes
DNA-Directed DNA Polymerase
Cytoplasm
Proteins
Chemical activation
Cells
Association reactions
DNA
Enzymes
DNA Ligase ATP

ASJC Scopus subject areas

  • Biochemistry

Cite this

Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress. / Das, Soumita; Chattopadhyay, Ranajoy; Bhakat, Kishor K.; Boldogh, Istvan; Kohno, Kimitoshi; Prasad, Rajendra; Wilson, Samuel H.; Hazra, Tapas.

In: Journal of Biological Chemistry, Vol. 282, No. 39, 28.09.2007, p. 28474-28484.

Research output: Contribution to journalArticle

Das, Soumita ; Chattopadhyay, Ranajoy ; Bhakat, Kishor K. ; Boldogh, Istvan ; Kohno, Kimitoshi ; Prasad, Rajendra ; Wilson, Samuel H. ; Hazra, Tapas. / Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 39. pp. 28474-28484.
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abstract = "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 IIIα and DNA polymerase β 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.",
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