The Large Subunit of Replication Factor C Interacts with the Histone Deacetylase, HDAC1

Lisa A Anderson,Neil D Perkins

doi:10.1074/jbc.m200513200

Lisa A Anderson, Neil D Perkins

Open Access

https://doi.org/10.1074/jbc.m200513200

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Abstract

Replication factor C (RFC) is a pentameric complex of five distinct subunits that functions as a clamp loader, facilitating the loading of proliferating cell nuclear antigen (PCNA) onto DNA during replication and repair. More recently the large subunit of RFC, RFC (p140), has been found to interact with the retinoblastoma (Rb) tumor suppressor and the CCAAT/enhancer-binding protein alpha (C/EBP alpha) transcription factor. We now report that RFC (p140) associates with histone deacetylase activity and interacts with histone deacetylase 1 (HDAC1). This complex is functional and when targeted to promoters as a Gal4 fusion, RFC (p140) is a strong, deacetylase-dependent repressor of transcription. Further analysis revealed that RFC (p140) contains two distinct transcriptional repression domains. Moreover, both of these domains interact separately with HDAC1.

Highlights

A common problem faced during the assembly of protein complexes on eukaryotic chromosomal DNA is the inhibitory effect of chromatin structure
The RbAp48 subunit of chromatin assembly factor 1 (CAF1), a protein complex that facilitates the assembly of nucleosomes onto newly replicated DNA [16, 17], has been identified as a protein known to interact with histone deacetylases and associate with the tumor suppressor protein Rb [16, 18, 19]
In this report we have demonstrated that the large subunit of replication factor C, RFC (p140), can interact with the histone deacetylase histone deacetylase 1 (HDAC1) through two distinct domains

Summary

Introduction

A common problem faced during the assembly of protein complexes on eukaryotic chromosomal DNA is the inhibitory effect of chromatin structure. In contrast to proteins with HAT activity, histone deacetylases are often associated with transcriptional repression [12, 13]. Proteins that participate in DNA replication and repair have been described associating with histone deacetylase activity.

Results

Conclusion