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Replication of damaged DNA in vitro is blocked by p53

Zhou, Jianmin and Prives, Carol (2003) Replication of damaged DNA in vitro is blocked by p53. Nucleic Acids Research, 31 (14). pp. 3881-3892. ISSN 0305-1048. http://resolver.caltech.edu/CaltechAUTHORS:ZHOnar03

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Abstract

The tumor suppressor protein p53 may have other roles and functions in addition to its well-documented ability to serve as a sequence-specific transcriptional activator in response to DNA damage. We showed previously that p53 can block the replication of polyomavirus origin-containing DNA (Py ori-DNA) in vitro when p53 binding sites are present on the late side of the Py ori. Here we have both further extended these observations and have also examined whether p53 might be able to bind directly to and inhibit the replication of damaged DNA. We found that p53 strongly inhibits replication of -irradiated Py ori-DNA and such inhibition requires both the central DNA binding domain and the extreme C-terminus of the p53 protein. An endogenous p53 binding site lies within the Py origin and is required for the ability of p53 to block initiation of replication from -irradiated Py ori-DNA, suggesting the possibility of DNA looping caused by p53 binding both non-specifically to sites of DNA damage and specifically to the endogenous site in the polyomavirus origin. Our results thus suggest the possibility that under some circumstances p53 might serve as a direct regulator of DNA replication and suggest as well an additional function for cooperation between its two autonomous DNA binding domains.


Item Type:Article
Additional Information:Copyright © 2003 Oxford University Press. Received as resubmission 28 April, 2003; accepted 20 May, 2003. Ella Freulich is thanked for excellent technical assistance. Scott Miller and Subarna Bhattacharyya are thanked for helpful suggestions. This work was supported by NIH grant CA58316 to C.P.
Subject Keywords:CELL-CYCLE ARREST; GLOBAL GENOMIC REPAIR; SEQUENCE-SPECIFIC DNA; LARGE T-ANTIGEN; WILD-TYPE P53; TRANSCRIPTIONAL ACTIVATION; TRANSACTIVATION ACTIVITY; BINDING ACTIVITY; TERMINAL DOMAIN; SV40 ORIGIN
Record Number:CaltechAUTHORS:ZHOnar03
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:ZHOnar03
Alternative URL:http://dx.doi.org/10.1093/nar/gkg468
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7225
Collection:CaltechAUTHORS
Deposited By: Lindsay Cleary
Deposited On:23 Jan 2007
Last Modified:26 Dec 2012 09:30

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