HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 15, 14694-14702, April 9, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/15/14694    most recent M313348200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Surguladze, N. Articles by Fried, M. G. Search for Related Content PubMed PubMed Citation Articles by Surguladze, N. Articles by Fried, M. G. Social Bookmarking                      What's this?

Interactions and Reactions of Ferritin with DNA^*

Nodar Surguladze, Khristy M. Thompson, John L. Beard, James R. Connor, and Michael G. Fried¶||

From the Departments of Neural and Behavioral Science and ^¶Biochemistry and Molecular Biology, the Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033 and the Department of Nutritional Sciences, the Pennsylvania State University, University Park, Pennsylvania 16802

Ferritin, normally considered a cytoplasmic iron-storage protein, is also found in the nuclei of some cells. There is no current agreement about its function(s) in this environment. Proposals include DNA protection, provision of iron to nuclear enzymes, and regulation of transcription initiation, but evidence for these functions is scanty. We have shown previously that H-ferritin subunits can be cross-linked to chromosomal DNA in vivo (Thompson, K. J., Fried, M. G., Ye, Z., Boyer, P., and Connor, J. R. (2002) J. Cell Sci. 115, 2165–2177). Here we describe systematic analyses of DNA binding and the covalent stability of DNA in the presence of ferritins from several different sources. Our data show that the H-subunit of human ferritin binds DNA, whereas neither the L-subunit nor the ferroxidase-deficient 222-mutant of the H-subunit has detectable binding activity. DNA binding is without significant preference for base composition, sequence, or the nature of DNA ends. H- and L-ferritins and ferritins of mixed subunit composition stimulate the conversion of superhelical plasmid DNA to the relaxed form. The sensitivity of this conversion to glycerol suggests that DNA is nicked by a free radical mechanism. The rate of nicking correlates with the iron content of the ferritin and is strongly inhibited by chelators. Ferritin-dependent nicking is characterized by a kinetic lag that is not seen in control reactions containing free iron species. These results suggest that the release of iron from ferritin is an important part of the nicking mechanism. The potential role of ferritin as a protector of the genome is discussed in the context of these results.

Received for publication, January 12, 2004 , and in revised form, January 12, 2004.

^* This work was supported by National Institutes of Health Grant DK54289. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed. Tel.: 717-531-5250; Fax: 717-533-9592; E-mail: mfried{at}psu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. Bhattacharyya and A. Grove The N-terminal Extensions of Deinococcus radiodurans Dps-1 Mediate DNA Major Groove Interactions as well as Assembly of the Dodecamer J. Biol. Chem., April 20, 2007; 282(16): 11921 - 11930. [Abstract] [Full Text] [PDF]

				R. Li, C. Luo, M. Mines, J. Zhang, and G.-H. Fan Chemokine CXCL12 Induces Binding of Ferritin Heavy Chain to the Chemokine Receptor CXCR4, Alters CXCR4 Signaling, and Induces Phosphorylation and Nuclear Translocation of Ferritin Heavy Chain J. Biol. Chem., December 8, 2006; 281(49): 37616 - 37627. [Abstract] [Full Text] [PDF]

				K. Iwasaki, E. L. MacKenzie, K. Hailemariam, K. Sakamoto, and Y. Tsuji Hemin-Mediated Regulation of an Antioxidant-Responsive Element of the Human Ferritin H Gene and Role of Ref-1 during Erythroid Differentiation of K562 Cells. Mol. Cell. Biol., April 1, 2006; 26(7): 2845 - 2856. [Abstract] [Full Text] [PDF]