CaltechAUTHORS
  A Caltech Library Service

Homologous regions of Fen1 and p21^(Cip1) compete for binding to the same site on PCNA: a potential mechanism to co-ordinate DNA replication and repair

Warbrick, Emma and Lane, David P. and Glover, David M. and Cox, Lynne S. (1997) Homologous regions of Fen1 and p21^(Cip1) compete for binding to the same site on PCNA: a potential mechanism to co-ordinate DNA replication and repair. Oncogene, 14 (19). pp. 2313-2321. ISSN 0950-9232. https://resolver.caltech.edu/CaltechAUTHORS:20201007-123359875

Full text is not posted in this repository. Consult Related URLs below.

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20201007-123359875

Abstract

Following genomic damage, the cessation of DNA replication is co-ordinated with onset of DNA repair; this co-ordination is essential to avoid mutation and genomic instability. To investigate these phenomena, we have analysed proteins that interact with PCNA, which is required for both DNA replication and repair. One such protein is p21^(Cip1), which inhibits DNA replication through its interaction with PCNA, while allowing repair to continue. We have identified an interaction between PCNA and the structure specific nuclease, Fen1, which is involved in DNA replication. Deletion analysis suggests that p21^(Cip1) and Fen1 bind to the same region of PCNA. Within Fen1 and its homologues a small region (10 amino acids) is sufficient for PCNA binding, which contains an 8 amino acid conserved PCNA-binding motif. This motif shares critical residues with the PCNA-binding region of p21^(Cip1). A PCNA binding peptide from p21^(Cip1) competes with Fen1 peptides for binding to PCNA, disrupts the Fen1-PCNA complex in replicating cell extracts, and concomitantly inhibits DNA synthesis. Competition between homologous regions of Fen1 and p21^(Cip1) for binding to the same site on PCNA may provide a mechanism to co-ordinate the functions of PCNA in DNA replication and repair.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/sj.onc.1201072DOIArticle
https://rdcu.be/b8cCPPublisherFree ReadCube access
ORCID:
AuthorORCID
Glover, David M.0000-0003-0956-0103
Alternate Title:Homologous regions of Fen1 and p21Cip1 compete for binding to the same site on PCNA: a potential mechanism to co-ordinate DNA replication and repair
Additional Information:© 1997 Stockton Press. Received 8 November 1996; revised 29 January 1997; accepted 29 January 1997. We would like to thank Fiona Cullen for assistance with DNA sequencing, Hiroyuki Ohkura and Peter Hall for helpful advice, Gus Reid for HPLC peptide purification, Angela Mehlert for mass spectrometry of the p21 nonapeptide, Fred Brewster for preparation of monoclonal antibodies, Jane Carter for assistance with densitometry, Byron Hann for critical reading of the manuscript, and Jo Murray for communicating results prior to publication. We are grateful to the Cancer Research Campaign for their generous support, and to the Royal Society of Edinburgh/ Caledonian Research Foundation for a personal research fellowship to LSC. DPL is a Gibb Fellow of the CRC and a Howard Hughes International Scholar.
Funders:
Funding AgencyGrant Number
Cancer Research CampaignUNSPECIFIED
Royal Society of EdinburghUNSPECIFIED
Caledonian Research FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:Fen1; p21^(Cip1); PCNA; DNA replication; DNA repair
Issue or Number:19
Record Number:CaltechAUTHORS:20201007-123359875
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201007-123359875
Official Citation:Warbrick, E., Lane, D., Glover, D. et al. Homologous regions of Fen1 and p21Cip1 compete for binding to the same site on PCNA: a potential mechanism to co-ordinate DNA replication and repair. Oncogene 14, 2313–2321 (1997). https://doi.org/10.1038/sj.onc.1201072
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105891
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:07 Oct 2020 21:34
Last Modified:07 Oct 2020 21:34

Repository Staff Only: item control page