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PMID: 11336696 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The large subunit of replication factor C promotes cell survival after DNA damage in an LxCxE motif- and Rb-dependent manner.

Molecular cell ·Vol. 7 ·No. 4 ·2001-04-00 ·Pages 715-27

Pennaneach V, Salles-Passador I, Munshi A, Brickner H, Regazzoni K, Dick F, Dyson N, Chen TT, Wang JY, Fotedar R, Fotedar A

Abstract

Retinoblastoma (Rb) protein promotes cell survival after DNA damage. We show here that the LxCxE binding site in Rb mediates both cell survival and cell-cycle arrest after DNA damage. Replication factor C (RF-C) complex plays an important role in DNA replication. We describe a novel function of the large subunit of RF-C in promoting cell survival after DNA damage. RF-Cp145 contains an LxCxE motif, and mutation of this motif abolishes the protective effect of RF-Cp145. The inability of wild-type RF-Cp145 to promote cell survival in Rb-null cells is rescued by Rb but not by Rb mutants defective in binding LxCxE proteins. RF-C thus enhances cell survival after DNA damage in an Rb-dependent manner.

MeSH Terms

Amino Acid Motifs Animals Binding Sites/physiology COS Cells Cell Cycle/genetics Cell Survival/genetics,radiation effects DNA Damage/genetics DNA Helicases DNA-Binding Proteins/chemistry,genetics,metabolism Female Histone Deacetylase 1 Histone Deacetylases/genetics,metabolism Homeodomain Proteins Humans Minor Histocompatibility Antigens Mutagenesis/physiology Nuclear Proteins/genetics,metabolism Proto-Oncogene Proteins c-bcl-2 Replication Protein C Repressor Proteins Retinoblastoma Protein/genetics,metabolism Saccharomyces cerevisiae Proteins Transcription Factors/genetics,metabolism Transfection Tumor Cells, Cultured Ultraviolet Rays Uterine Cervical Neoplasms

Chemicals

BCL2-related protein A1 DNA-Binding Proteins Homeodomain Proteins MATA1 protein, S cerevisiae Minor Histocompatibility Antigens Nuclear Proteins Proto-Oncogene Proteins c-bcl-2 Repressor Proteins Retinoblastoma Protein Saccharomyces cerevisiae Proteins Transcription Factors HDAC1 protein, human Histone Deacetylase 1 Histone Deacetylases SMARCA4 protein, human DNA Helicases Replication Protein C

Authors & Affiliations

11 authors, click to expand affiliations / ORCID

Pennaneach V

Sidney Kimmel Cancer Center, 10835 Altman Road, San Diego, CA 92121, USA.

Salles-Passador I

Munshi A

Brickner H

Regazzoni K

Dick F

Dyson N

Chen T T

Wang J Y

Fotedar R

Fotedar A

Article Info

Journal

Molecular cell

Abbr.

Mol Cell

ISSN

1097-2765

DOI

10.1016/s1097-2765(01)00217-9

Published

2001-04-00

Pages

715-27

Language

English

Region

United States

NLM ID

9802571

Subset

Grants

NCI NIH HHS · R01 CA058320 · United States

NIAID NIH HHS · AI31453 · United States

NCI NIH HHS · CA74435 · United States

External Links

PubMed source DOI: 10.1016/s1097-2765(01)00217-9 View journal details

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The large subunit of replication factor C promotes cell survival after DNA damage in an LxCxE motif- and Rb-dependent manner.

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