A nuclear 3'-5' exonuclease proofreads for the exonuclease-deficient DNA polymerase alpha - PubMed (original) (raw)
A nuclear 3'-5' exonuclease proofreads for the exonuclease-deficient DNA polymerase alpha
Kevin R Brown et al. DNA Repair (Amst). 2002.
Abstract
DNA replication is a highly accurate process designed to duplicate the entire genome of a cell during each cell division. The accuracy of DNA replication is derived from the balance between three important components: base selectivity by the replicative DNA polymerases (pols), exonucleolytic proofreading, and post-replicative mismatch repair. Previously we identified a human 3'-5' exonuclease (exoN) whose properties suggested it may function as a proofreader for the exonuclease-deficient replicative DNA pol alpha. Purified exoN has no associated pol activity and catalyzes removal of mispaired nucleotides from DNA duplexes. Consistent with previous reports, it was found that mammalian pol alpha is inefficient at extending from mispaired DNA terminals. However, in similar reactions that included exoN, there was a 4.4-15.7-fold increase in pol alpha-catalyzed elongation from mispaired base pairs. In contrast, exoN did not have a dramatic impact on the ability of exonuclease-deficient variants of Klenow (K-) and T7 polymerase to catalyze extension from mispaired DNA. Continuous DNA replication catalyzed by either pol alpha or K- generated base substitutions at a frequency of 24.3x10(-4) and 38x10(-4), respectively. ExoN restored error-free DNA replication in reactions with pol alpha whereas it did not significantly improve the accuracy of K-. These results are consistent with a functional interaction between exoN and pol alpha to ensure accurate DNA replication.
Similar articles
- Contribution of the 3'- to 5'-exonuclease activity of herpes simplex virus type 1 DNA polymerase to the fidelity of DNA synthesis.
Song L, Chaudhuri M, Knopf CW, Parris DS. Song L, et al. J Biol Chem. 2004 Apr 30;279(18):18535-43. doi: 10.1074/jbc.M309848200. Epub 2004 Feb 23. J Biol Chem. 2004. PMID: 14982924 - Fidelity of mammalian DNA replication and replicative DNA polymerases.
Thomas DC, Roberts JD, Sabatino RD, Myers TW, Tan CK, Downey KM, So AG, Bambara RA, Kunkel TA. Thomas DC, et al. Biochemistry. 1991 Dec 24;30(51):11751-9. doi: 10.1021/bi00115a003. Biochemistry. 1991. PMID: 1751492 - Fidelity of DNA replication-a matter of proofreading.
Bębenek A, Ziuzia-Graczyk I. Bębenek A, et al. Curr Genet. 2018 Oct;64(5):985-996. doi: 10.1007/s00294-018-0820-1. Epub 2018 Mar 2. Curr Genet. 2018. PMID: 29500597 Free PMC article. Review. - Extrinsic proofreading.
Zhou ZX, Kunkel TA. Zhou ZX, et al. DNA Repair (Amst). 2022 Sep;117:103369. doi: 10.1016/j.dnarep.2022.103369. Epub 2022 Jul 4. DNA Repair (Amst). 2022. PMID: 35850061 Free PMC article. Review.
Cited by
- MIF is a 3' flap nuclease that facilitates DNA replication and promotes tumor growth.
Wang Y, Chen Y, Wang C, Yang M, Wang Y, Bao L, Wang JE, Kim B, Chan KY, Xu W, Capota E, Ortega J, Nijhawan D, Li GM, Luo W, Wang Y. Wang Y, et al. Nat Commun. 2021 May 19;12(1):2954. doi: 10.1038/s41467-021-23264-z. Nat Commun. 2021. PMID: 34012010 Free PMC article. - DNA polymerase δ proofreads errors made by DNA polymerase ε.
Bulock CR, Xing X, Shcherbakova PV. Bulock CR, et al. Proc Natl Acad Sci U S A. 2020 Mar 17;117(11):6035-6041. doi: 10.1073/pnas.1917624117. Epub 2020 Mar 2. Proc Natl Acad Sci U S A. 2020. PMID: 32123096 Free PMC article. - The role of DNA exonucleases in protecting genome stability and their impact on ageing.
Mason PA, Cox LS. Mason PA, et al. Age (Dordr). 2012 Dec;34(6):1317-40. doi: 10.1007/s11357-011-9306-5. Epub 2011 Sep 23. Age (Dordr). 2012. PMID: 21948156 Free PMC article. Review. - Types and frequencies of sequencing errors in methyl-filtered and high c0t maize genome survey sequences.
Fu Y, Hsia AP, Guo L, Schnable PS. Fu Y, et al. Plant Physiol. 2004 Aug;135(4):2040-5. doi: 10.1104/pp.104.041640. Epub 2004 Aug 6. Plant Physiol. 2004. PMID: 15299135 Free PMC article. - Gene-targeted mice lacking the Trex1 (DNase III) 3'-->5' DNA exonuclease develop inflammatory myocarditis.
Morita M, Stamp G, Robins P, Dulic A, Rosewell I, Hrivnak G, Daly G, Lindahl T, Barnes DE. Morita M, et al. Mol Cell Biol. 2004 Aug;24(15):6719-27. doi: 10.1128/MCB.24.15.6719-6727.2004. Mol Cell Biol. 2004. PMID: 15254239 Free PMC article.