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Replication protein A as a major eukaryotic single-stranded DNA-binding protein and its role in DNA repair

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Abstract

Replication protein A (RPA) is a key regulator of eukaryotic DNA metabolism. RPA is a highly conserved heterotrimeric protein and contains multiple oligonucleotide/oligosaccharide-binding folds. The major RPA function is binding to single-stranded DNA (ssDNA) intermediates forming in DNA replication, repair, and recombination. Although binding ssDNA with high affinity, RPA can rapidly diffuse along ssDNA and destabilizes the DNA secondary structure. A highly dynamic RPA binding to ssDNA allows other proteins to access ssDNA and to displace RPA from the RPA–ssDNA complex. As has been shown recently, RPA in complex with ssDNA is posttranslationally modified in response to DNA damage. These modifications modulate the RPA interactions with its protein partners and control the DNA damage signaling pathways. The review considers up-to-date data on the RPA function as an active coordinator of ssDNA intermediate processing within DNA metabolic pathways, DNA repair in particular.

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Abbreviations

dsDNA:

double-stranded DNA

ssDNA:

singlestranded DNA

ATR:

ataxia telangiectasia and Rad3-related protein

NER:

nucleotide excision repair

OB domain:

oligosaccharide/oligonucleotide-binding domain

polprim:

DNA polymerase α–primase complex

RPA:

replication protein A

hsRPA:

human (Homo sapiens) RPA

umRPA:

Ustilago maydis RPA

SSB:

ssDNA binding

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Original Russian Text © Y.S. Krasikova, N.I. Rechkunova, O.I. Lavrik, 2016, published in Molekulyarnaya Biologiya, 2016, Vol. 50, No. 5, pp. 735–750.

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Krasikova, Y.S., Rechkunova, N.I. & Lavrik, O.I. Replication protein A as a major eukaryotic single-stranded DNA-binding protein and its role in DNA repair. Mol Biol 50, 649–662 (2016). https://doi.org/10.1134/S0026893316030080

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