Replication protein A

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Replication protein A
1L1O Replication protein A.png
This is an image of human Replication protein A. From PDB: 1L1OProteopedia protein A Replication protein A
Gene Chromosomal
Replication protein A1 RPA1 Chr. 17 p13.3
Replication protein A2 RPA2 Chr. 1 p35.3
Replication protein A3 RPA3 Chr. 7 p21.3

Replication protein A (RPA) is the major protein that binds to single-stranded DNA (ssDNA) in eukaryotic cells.[1][2] In vitro, RPA shows a much higher affinity for ssDNA than RNA or double-stranded DNA.[3]

During DNA replication, RPA prevents single-stranded DNA (ssDNA) from winding back on itself or from forming secondary structures. This keeps DNA unwound for the polymerase to replicate it. RPA also binds to ssDNA during the initial phase of homologous recombination, an important process in DNA repair and prophase I of meiosis.

Hypersensitivity to DNA damaging agents can be caused by mutations in the RPA gene.[4] Like its role in DNA replication, this keeps ssDNA from binding to itself (self-complementizing) so that the resulting nucleoprotein filament can then be bound by Rad51 and its cofactors.[5]

RPA also binds to DNA during the nucleotide excision repair process. This binding stabilizes the repair complex during the repair process. A bacterial homolog is called single-strand binding protein (SSB).


RPA is a heterotrimer, composed of the subunits RPA1 (70kDa subunit), RPA2 (32kDa subunit) and RPA3 (14kDa subunit). The three RPA subunits contain four OB-folds (oligonucleotide/oligosaccharide binding) that bind RPA to single-stranded DNA.[3][2] RPA shares many features with the CST Complex heterotrimer, although RPA has a more uniform 1:1:1 stoichiometry.[6]

See also[edit]


  1. ^ Wold, MS (1997). "Replication protein A: heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism". Annual Review of Biochemistry. 66 (1): 61–92. doi:10.1146/annurev.biochem.66.1.61. PMID 9242902. 
  2. ^ a b Chen R, Wold MS (2014). "Replication protein A: single-stranded DNA's first responder: dynamic DNA-interactions allow replication protein A to direct single-strand DNA intermediates into different pathways for synthesis or repair". BioEssays. 36 (12): 1156–1161. doi:10.1002/bies.201400107. PMC 4629251Freely accessible. PMID 25171654. 
  3. ^ a b Flynn RL, Zou L (2010). "Oligonucleotide/oligosaccharide-binding fold proteins: a growing family of genome guardians". Critical Reviews in Biochemistry and Molecular Biology. 45 (4): 266–275. doi:10.3109/10409238.2010.488216. PMC 2906097Freely accessible. PMID 20515430. 
  4. ^ Zou, Yue; Liu, Yiyong; Wu, Xiaoming; Shell, Steven M. (2006-08-01). "Functions of human replication protein A (RPA): from DNA replication to DNA damage and stress responses". Journal of Cellular Physiology. 208 (2): 267–273. doi:10.1002/jcp.20622. ISSN 0021-9541. PMC 3107514Freely accessible. PMID 16523492. 
  5. ^ Xuan, L; Wolf-Dietrich, H (2008). "Homologous recombination in DNA repair and DNA damage tolerance". Cell Research. 18 (99): 99–113. doi:10.1038/cr.2008.1. PMC 3087377Freely accessible. PMID 18166982. 
  6. ^ Lue NF, Zhou R, Chico L, Mao N, Steinberg-Neifach O, Ha T (2013). "The telomere capping complex CST has an unusual stoichiometry, makes multipartite interaction with G-Tails, and unfolds higher-order G-tail structures" (PDF). PLOS Genetics. 9 (1): e1003145. doi:10.1371/journal.pgen.1003145. PMC 3536697Freely accessible. PMID 23300477.