Journal article
Cellular Functions of Human RPA1: MULTIPLE ROLES OF DOMAINS IN REPLICATION, REPAIR, AND CHECKPOINTS
The Journal of biological chemistry, Vol.283(27), pp.19095-19111
07/04/2008
DOI: 10.1074/jbc.M800881200
PMCID: PMC2441558
PMID: 18469000
Abstract
In eukaryotes, the single strand DNA (ssDNA)-binding protein, replication
protein A (RPA), is essential for DNA replication, repair, and recombination.
RPA is composed of the following three subunits: RPA1, RPA2, and RPA3. The
RPA1 subunit contains four structurally related domains and is responsible for
high affinity ssDNA binding. This study uses a depletion/replacement strategy
in human cells to reveal the contributions of each domain to RPA cellular
functions. Mutations that substantially decrease ssDNA binding activity do not
necessarily disrupt cellular RPA function. Conversely, mutations that only
slightly affect ssDNA binding can dramatically affect cellular function. The N
terminus of RPA1 is not necessary for DNA replication in the cell; however,
this region is important for the cellular response to DNA damage. Highly
conserved aromatic residues in the high affinity ssDNA-binding domains are
essential for DNA repair and cell cycle progression. Our findings suggest that
as long as a threshold of RPA-ssDNA binding activity is met, DNA replication
can occur and that an RPA activity separate from ssDNA binding is essential
for function in DNA repair.
Details
- Title: Subtitle
- Cellular Functions of Human RPA1: MULTIPLE ROLES OF DOMAINS IN REPLICATION, REPAIR, AND CHECKPOINTS
- Creators
- Stuart J Haring - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Aaron C Mason - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Sara K Binz - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Marc S Wold - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.283(27), pp.19095-19111
- DOI
- 10.1074/jbc.M800881200
- PMID
- 18469000
- PMCID
- PMC2441558
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology
- Language
- English
- Date published
- 07/04/2008
- Academic Unit
- Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984024549202771
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