Eukaryotic single-stranded DNA binding proteins: central factors in genome stability

Sub-cellular Biochemistry
Sandra BroderickHeinz-Peter Nasheuer

Abstract

The single-stranded DNA binding proteins (SSBs) are required to maintain the integrity of the genome in all organisms. Replication protein A (RPA) is a nuclear SSB protein found in all eukaryotes and is required for multiple processes in DNA metabolism such as DNA replication, DNA repair, DNA recombination, telomere maintenance and DNA damage signalling. RPA is a heterotrimeric complex, binds ssDNA with high affinity, and interacts specifically with multiple proteins to fulfil its function in eukaryotes. RPA is phosphorylated in a cell cycle and DNA damage-dependent manner with evidence suggesting that phosphorylation has an important function in modulating the cellular DNA damage response. Considering the DNA-binding properties of RPA a mechanism of "molecular counting" to initiate DNA damage-dependent signalling is discussed. Recently a human homologue to the RPA2 subunit, called RPA4, was discovered and RPA4 can substitute for RPA2 in the RPA complex resulting in an "alternative" RPA (aRPA), which can bind to ssDNA with similar affinity as canonical RPA. Additional human SSBs, hSSB1 and hSSB2, were recently identified, with hSSB1 being localized in the nucleus and having implications in DNA repair. Mitochondrial SSBs (mtSSBs...Continue Reading

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Related Concepts

SSBP1 gene
DNA Replication Factor A Complex Location
DNA Repair
DNA, Mitochondrial
NABP1 gene
Genomic Stability
Response to DNA Damage Stimulus
Protein Phosphorylation
Recombination, Genetic
Cell Nucleus

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