RPA4 and RPA2/4 Hybrids for the Prevention of Aberrant Cell Growth
Substitution of all or part of Replication Protein A-2 (RPA2) with RPA4 in the RPA complex inhibits a cell's ability to replicate.
UIRF Case #:07068
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Mason AC, Haring SJ, Pryor JM, Staloch CA, Gan TF, Wold MS. An alternative form of replication protein a prevents viral replication in vitro. J Biol Chem. 2009 Feb 20;284(8):5324-31.
Level of Development
General: in vitro
Researchers at the University of Iowa have identified an endogenous human protein that is able to abrogate DNA replication and cellular proliferation activities when expressed in actively replicating cells. This novel protein, called RPA4, has been shown to share 47% identity with RPA2 at the genetic level and can substitute for RPA2 in the RPA trimeric complex. When this substitution occurs, the RPA complex no longer recruits replication machinery to ssDNA, but is still able to mediate the activities of DNA repair machinery. This results in the retention of genomic DNA maintenance activities and the loss of cellular replication abilities in these cells. The endogenous expression of RPA4 in adult subjects has only been identified in colon mucosa tissues and studies have shown that expression of RPA4 is far below that of RPA1 and RPA2 in proliferating cultured cells.
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