| Structural highlights
Disease
[UNG_HUMAN] Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM:608106]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.[1] [2]
Function
[RFA2_HUMAN] Required for DNA recombination, repair and replication. The activity of RP-A is mediated by single-stranded DNA binding and protein interactions. Required for the efficient recruitment of the DNA double-strand break repair factor RAD51 to chromatin in response to DNA damage.[3] [4] [5] [6] Functions as component of the alternative replication protein A complex (aRPA). aRPA binds single-stranded DNA and probably plays a role in DNA repair; it does not support chromosomal DNA replication and cell cycle progression through S-phase. In vitro, aRPA cannot promote efficient priming by DNA polymerase alpha but supports DNA polymerase delta synthesis in the presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange.[7] [8] [9] [10] [UNG_HUMAN] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Replication protein A (RPA), the nuclear ssDNA-binding protein in eukaryotes, is essential to DNA replication, recombination, and repair. We have shown that a globular domain at the C terminus of subunit RPA32 contains a specific surface that interacts in a similar manner with the DNA repair enzyme UNG2 and repair factors XPA and RAD52, each of which functions in a different repair pathway. NMR structures of the RPA32 domain, free and in complex with the minimal interaction domain of UNG2, were determined, defining a common structural basis for linking RPA to the nucleotide excision, base excision, and recombinational pathways of repairing damaged DNA. Our findings support a hand-off model for the assembly and coordination of different components of the DNA repair machinery.
Structural basis for the recognition of DNA repair proteins UNG2, XPA, and RAD52 by replication factor RPA.,Mer G, Bochkarev A, Gupta R, Bochkareva E, Frappier L, Ingles CJ, Edwards AM, Chazin WJ Cell. 2000 Oct 27;103(3):449-56. PMID:11081631[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Imai K, Slupphaug G, Lee WI, Revy P, Nonoyama S, Catalan N, Yel L, Forveille M, Kavli B, Krokan HE, Ochs HD, Fischer A, Durandy A. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol. 2003 Oct;4(10):1023-8. Epub 2003 Sep 7. PMID:12958596 doi:http://dx.doi.org/10.1038/ni974
- ↑ Kavli B, Andersen S, Otterlei M, Liabakk NB, Imai K, Fischer A, Durandy A, Krokan HE, Slupphaug G. B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil. J Exp Med. 2005 Jun 20;201(12):2011-21. PMID:15967827 doi:10.1084/jem.20050042
- ↑ Weisshart K, Pestryakov P, Smith RW, Hartmann H, Kremmer E, Lavrik O, Nasheuer HP. Coordinated regulation of replication protein A activities by its subunits p14 and p32. J Biol Chem. 2004 Aug 20;279(34):35368-76. Epub 2004 Jun 17. PMID:15205463 doi:10.1074/jbc.M403825200
- ↑ 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. doi: 10.1074/jbc.M808963200. Epub 2008, Dec 29. PMID:19116208 doi:10.1074/jbc.M808963200
- ↑ Kemp MG, Mason AC, Carreira A, Reardon JT, Haring SJ, Borgstahl GE, Kowalczykowski SC, Sancar A, Wold MS. An alternative form of replication protein a expressed in normal human tissues supports DNA repair. J Biol Chem. 2010 Feb 12;285(7):4788-97. doi: 10.1074/jbc.M109.079418. Epub 2009 , Dec 7. PMID:19996105 doi:10.1074/jbc.M109.079418
- ↑ Lee DH, Pan Y, Kanner S, Sung P, Borowiec JA, Chowdhury D. A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination. Nat Struct Mol Biol. 2010 Mar;17(3):365-72. doi: 10.1038/nsmb.1769. Epub 2010 Feb, 14. PMID:20154705 doi:10.1038/nsmb.1769
- ↑ Weisshart K, Pestryakov P, Smith RW, Hartmann H, Kremmer E, Lavrik O, Nasheuer HP. Coordinated regulation of replication protein A activities by its subunits p14 and p32. J Biol Chem. 2004 Aug 20;279(34):35368-76. Epub 2004 Jun 17. PMID:15205463 doi:10.1074/jbc.M403825200
- ↑ 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. doi: 10.1074/jbc.M808963200. Epub 2008, Dec 29. PMID:19116208 doi:10.1074/jbc.M808963200
- ↑ Kemp MG, Mason AC, Carreira A, Reardon JT, Haring SJ, Borgstahl GE, Kowalczykowski SC, Sancar A, Wold MS. An alternative form of replication protein a expressed in normal human tissues supports DNA repair. J Biol Chem. 2010 Feb 12;285(7):4788-97. doi: 10.1074/jbc.M109.079418. Epub 2009 , Dec 7. PMID:19996105 doi:10.1074/jbc.M109.079418
- ↑ Lee DH, Pan Y, Kanner S, Sung P, Borowiec JA, Chowdhury D. A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination. Nat Struct Mol Biol. 2010 Mar;17(3):365-72. doi: 10.1038/nsmb.1769. Epub 2010 Feb, 14. PMID:20154705 doi:10.1038/nsmb.1769
- ↑ Mer G, Bochkarev A, Gupta R, Bochkareva E, Frappier L, Ingles CJ, Edwards AM, Chazin WJ. Structural basis for the recognition of DNA repair proteins UNG2, XPA, and RAD52 by replication factor RPA. Cell. 2000 Oct 27;103(3):449-56. PMID:11081631
|
