Post-replicative base excision repair in replication foci
- PMID: 10393198
- PMCID: PMC1171460
- DOI: 10.1093/emboj/18.13.3834
Post-replicative base excision repair in replication foci
Abstract
Base excision repair (BER) is initiated by a DNA glycosylase and is completed by alternative routes, one of which requires proliferating cell nuclear antigen (PCNA) and other proteins also involved in DNA replication. We report that the major nuclear uracil-DNA glycosylase (UNG2) increases in S phase, during which it co-localizes with incorporated BrdUrd in replication foci. Uracil is rapidly removed from replicatively incorporated dUMP residues in isolated nuclei. Neutralizing antibodies to UNG2 inhibit this removal, indicating that UNG2 is the major uracil-DNA glycosylase responsible. PCNA and replication protein A (RPA) co-localize with UNG2 in replication foci, and a direct molecular interaction of UNG2 with PCNA (one binding site) and RPA (two binding sites) was demonstrated using two-hybrid assays, a peptide SPOT assay and enzyme-linked immunosorbent assays. These results demonstrate rapid post-replicative removal of incorporated uracil by UNG2 and indicate the formation of a BER complex that contains UNG2, RPA and PCNA close to the replication fork.
Similar articles
-
The UNG2 Arg88Cys variant abrogates RPA-mediated recruitment of UNG2 to single-stranded DNA.DNA Repair (Amst). 2012 Jun 1;11(6):559-69. doi: 10.1016/j.dnarep.2012.03.006. Epub 2012 Apr 20. DNA Repair (Amst). 2012. PMID: 22521144
-
Different organization of base excision repair of uracil in DNA in nuclei and mitochondria and selective upregulation of mitochondrial uracil-DNA glycosylase after oxidative stress.Neuroscience. 2007 Apr 14;145(4):1201-12. doi: 10.1016/j.neuroscience.2006.10.010. Epub 2006 Nov 13. Neuroscience. 2007. PMID: 17101234
-
Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place predominantly by short-patch repair both in proliferating and growth-arrested cells.Nucleic Acids Res. 2004 Oct 12;32(18):5486-98. doi: 10.1093/nar/gkh872. Print 2004. Nucleic Acids Res. 2004. PMID: 15479784 Free PMC article.
-
Uracil in DNA--occurrence, consequences and repair.Oncogene. 2002 Dec 16;21(58):8935-48. doi: 10.1038/sj.onc.1205996. Oncogene. 2002. PMID: 12483510 Review.
-
Properties and functions of human uracil-DNA glycosylase from the UNG gene.Prog Nucleic Acid Res Mol Biol. 2001;68:365-86. doi: 10.1016/s0079-6603(01)68112-1. Prog Nucleic Acid Res Mol Biol. 2001. PMID: 11554311 Review.
Cited by
-
Nucleotide excision repair is associated with the replisome and its efficiency depends on a direct interaction between XPA and PCNA.PLoS One. 2012;7(11):e49199. doi: 10.1371/journal.pone.0049199. Epub 2012 Nov 13. PLoS One. 2012. PMID: 23152873 Free PMC article.
-
RPA guides UNG to uracil in ssDNA to facilitate antibody class switching and repair of mutagenic uracil at the replication fork.Nucleic Acids Res. 2024 Jan 25;52(2):784-800. doi: 10.1093/nar/gkad1115. Nucleic Acids Res. 2024. PMID: 38000394 Free PMC article.
-
Replication fork velocities at adjacent replication origins are coordinately modified during DNA replication in human cells.Mol Biol Cell. 2007 Aug;18(8):3059-67. doi: 10.1091/mbc.e06-08-0689. Epub 2007 May 23. Mol Biol Cell. 2007. PMID: 17522385 Free PMC article.
-
The uracil DNA glycosylase UdgB of Mycobacterium smegmatis protects the organism from the mutagenic effects of cytosine and adenine deamination.J Bacteriol. 2009 Oct;191(20):6312-9. doi: 10.1128/JB.00613-09. Epub 2009 Aug 14. J Bacteriol. 2009. PMID: 19684133 Free PMC article.
-
A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification.DNA Repair (Amst). 2007 Jun 1;6(6):695-711. doi: 10.1016/j.dnarep.2007.01.009. Epub 2007 Mar 6. DNA Repair (Amst). 2007. PMID: 17337257 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous
