Phosphorylation of RPA2 by CDC2 kinase

Stable Identifier
R-GGA-265936
Type
Reaction [transition]
Species
Gallus gallus
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Replication protein A (RPA) is a heterotrimeric single stranded DNA (ssDNA)-binding protein with essential functions in DNA replication, DNA repair and DNA recombination. RPA binds with rapid kinetics and high-affinity to ssDNA with 5’ to 3’ molecular polarity. The DNA-binding domains (DBDs) A and B on the RPA1 subunit comprise the high-affinity ssDNA activity, which is also responsible for DNA unwinding. Phosphorylation of the RPA2 subunit by chicken cdc2 kinase facilitated DNA unwinding, suggesting that this post-translational modification might be important for modulating this RPA activity. RPA coated ssDNA has also been implicated as one of the triggers for intra-S phase checkpoint activation. Phosphorylation of RPA occurs in cells with damaged DNA or stalled replication forks. The human RPA1 and/or RPA2 subunits can be phosphorylated by purified checkpoint kinases ATR and ATM, the related DNA-PK, and Chk1. RPA2 is also a substrate for cyclin B-Cdc2 and cyclin A-Cdk1. Chk1 phosphorylated RPA1 shows reduced ssDNA binding activity, and binding of RPA to ssDNA blocks Chk1 phosphorylation. Further, ssDNA stimulates RPA2 phosphorylation by ATR that leads to a disassembly of the RPA heterotrimer. Phosphorylation of RPA by cyclin-Cdk has been shown to be essential for proper DNA repair in interphase cells.

Literature References
PubMed ID Title Journal Year
16412704 Phosphorylation of replication protein A by S-phase checkpoint kinases

Liu, JS, Kuo, SR, Melendy, T

DNA Repair (Amst) 2006
8396234 DNA unwinding by replication protein A is a property of the 70 kDa subunit and is facilitated by phosphorylation of the 32 kDa subunit

Georgaki, A, Hübscher, U

Nucleic Acids Res 1993
17928296 Sequential and synergistic modification of human RPA stimulates chromosomal DNA repair

Anantha, RW, Vassin, VM, Borowiec, JA

J Biol Chem 2007
10336450 Phosphorylation of replication protein A middle subunit (RPA32) leads to a disassembly of the RPA heterotrimer

Treuner, K, Findeisen, M, Strausfeld, U, Knippers, R

J Biol Chem 1999
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Catalyst Activity
Title
protein serine/threonine kinase activity of CDC2 kinase, Cell division control protein 2 homolog [nucleoplasm]
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