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

J. Biol. Chem., Vol. 280, Issue 52, 42568-42572, December 30, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/52/42568    most recent M506348200v1 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 Subramanian, D. Articles by Griffith, J. D. Search for Related Content PubMed PubMed Citation Articles by Subramanian, D. Articles by Griffith, J. D. Social Bookmarking                      What's this?

p53 Monitors Replication Fork Regression by Binding to "Chickenfoot" Intermediates^*

From the Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599

The tumor suppressor protein, p53, utilizes multiple mechanisms to ensure faithful transmission of the genome including regulation of DNA replication, repair, and recombination. Monitoring these pathways may involve direct binding of p53 to the DNA intermediates of these processes. In this study, we generated templates resembling stalled replication forks and utilized electron microscopy to examine p53 interactions with these substrates. Our results show that p53 bound with high affinity to the junction of stalled forks, whereas two cancer-derived p53 mutants showed weak binding. Additionally, some of the templates were rearranged to form "chickenfoot" structures in the presence of p53. These were mostly formed due to p53 trapping intermediates of spontaneous fork regression; however, in a small population, the protein appeared to be promoting their formation. Collectively, these results demonstrate the importance of sequence-independent binding in p53-mediated maintenance of genomic integrity.

Received for publication, June 10, 2005 , and in revised form, September 29, 2005.

^* This work was supported by the Ellison Medical Foundation and National Institutes of Health Grants CA19014 and GM31819. 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.

¹ To whom correspondence may be addressed: 119 Lineberger Comprehensive Cancer Center, CB 7295, Mason Farm Rd., Chapel Hill, NC 27599. Tel.: 919-966-2151; Fax: 919-966-3015; E-mail: jdg{at}med.unc.edu.

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

This article has been cited by other articles:

				S. A. Compton, G. Tolun, A. S. Kamath-Loeb, L. A. Loeb, and J. D. Griffith The Werner Syndrome Protein Binds Replication Fork and Holliday Junction DNAs as an Oligomer J. Biol. Chem., September 5, 2008; 283(36): 24478 - 24483. [Abstract] [Full Text] [PDF]

				A. Pamidi, R. Cardoso, A. Hakem, E. Matysiak-Zablocki, A. Poonepalli, L. Tamblyn, B. Perez-Ordonez, M. P. Hande, O. Sanchez, and R. Hakem Functional Interplay of p53 and Mus81 in DNA Damage Responses and Cancer Cancer Res., September 15, 2007; 67(18): 8527 - 8535. [Abstract] [Full Text] [PDF]

				N. G. Nossal, A. M. Makhov, P. D. Chastain II, C. E. Jones, and J. D. Griffith Architecture of the Bacteriophage T4 Replication Complex Revealed with Nanoscale Biopointers J. Biol. Chem., January 12, 2007; 282(2): 1098 - 1108. [Abstract] [Full Text] [PDF]

				N. Fouche, A. J. Cesare, S. Willcox, S. Ozgur, S. A. Compton, and J. D. Griffith The Basic Domain of TRF2 Directs Binding to DNA Junctions Irrespective of the Presence of TTAGGG Repeats J. Biol. Chem., December 8, 2006; 281(49): 37486 - 37495. [Abstract] [Full Text] [PDF]

				N. Fouche, S. Ozgur, D. Roy, and J. D. Griffith Replication fork regression in repetitive DNAs Nucleic Acids Res., November 6, 2006; 34(20): 6044 - 6050. [Abstract] [Full Text] [PDF]