title: Microsatellite instability in Arabidopsis increases with plant development.
abstract: Plant development consists of the initial phase of intensive cell division followed by continuous genome endoreduplication, cell growth, and elongation. The maintenance of genome stability under these conditions is the main task performed by DNA repair and genome surveillance mechanisms. Our previous work showed that the rate of homologous recombination repair in older plants decreases. We hypothesized that this age-dependent decrease in the recombination rate is paralleled with other changes in DNA repair capacity. Here, we analyzed microsatellite stability using transgenic Arabidopsis (Arabidopsis thaliana) plants that carry the nonfunctional β-glucuronidase gene disrupted by microsatellite repeats. We found that microsatellite instability increased dramatically with plant age. We analyzed the contribution of various mechanisms to microsatellite instability, including replication errors and mistakes of DNA repair mechanisms such as mismatch repair, excision repair, and strand break repair. Analysis of total DNA polymerase activity using partially purified protein extracts showed an age-dependent decrease in activity and an increase in fidelity. Analysis of the steady-state RNA level of DNA replicative polymerases α, δ, Pol I-like A, and Pol I-like B and the expression of mutS homolog 2 (Msh2) and Msh6 showed an age-dependent decrease. An in vitro repair assay showed lower efficiency of nonhomologous end joining in older plants, paralleled by an increase in Ku70 gene expression. Thus, we assume that the more frequent involvement of nonhomologous end joining in strand break repair and the less efficient end-joining repair together with lower levels of mismatch repair activities may be the main contributors to the observed age-dependent increase in microsatellite instability.
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.
authors.forename: Andrey
authors.initials: A
authors.lastname: Golubov
authors.forename: Youli
authors.initials: Y
authors.lastname: Yao
authors.forename: Priti
authors.initials: P
authors.lastname: Maheshwari
authors.forename: Andriy
authors.initials: A
authors.lastname: Bilichak
authors.forename: Alex
authors.initials: A
authors.lastname: Boyko
authors.forename: François
authors.initials: F
authors.lastname: Belzile
authors.forename: Igor
authors.initials: I
authors.lastname: Kovalchuk
mesh_terms: D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D018744:DNA, Plant / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D018506:Gene Expression Regulation, Plant; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D009154:Mutation; D030821:Plants, Genetically Modified / Q000235:genetics; D013997:Time Factors
chemical_list: D018744:DNA, Plant; D004259:DNA-Directed DNA Polymerase; D045643:DNA Repair Enzymes
references.citation: Plant Cell. 2002 Jan;14(1):263-73
references.pmid: 11826311
references.citation: DNA Repair (Amst). 2002 Aug 6;1(8):579-600
references.pmid: 12509283
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Annu Rev Biochem. 2000;69:497-529
references.pmid: 10966467
references.citation: Nucleic Acids Res. 2007;35(22):7466-74
references.pmid: 17913742
references.citation: Exp Mol Med. 2006 Dec 31;38(6):686-93
references.pmid: 17202845
references.citation: Annu Rev Plant Physiol Plant Mol Biol. 1996 Jun;47:75-100
references.pmid: 15012283
references.citation: Plant Mol Biol. 2004 Oct;56(3):339-49
references.pmid: 15604748
references.citation: Biochemistry (Mosc). 2004 Apr;69(4):429-34
references.pmid: 15170380
references.citation: Exp Gerontol. 2004 Apr;39(4):507-15
references.pmid: 15050284
references.citation: Mutat Res. 2002 Mar 20;500(1-2):135-45
references.pmid: 11890943
references.citation: DNA Repair (Amst). 2007 Dec 1;6(12):1740-8
references.pmid: 17686666
references.citation: Nature. 2000 Dec 14;408(6814):796-815
references.pmid: 11130711
references.citation: Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1614-8
references.pmid: 8434025
references.citation: Crit Rev Biochem Mol Biol. 2001;36(4):337-97
references.pmid: 11563486
references.citation: Nucleic Acids Res. 2003 Oct 15;31(20):6027-34
references.pmid: 14530450
references.citation: Bioessays. 1990 Feb;12(2):74-9
references.pmid: 2188652
references.citation: J Exp Bot. 2006;57(9):1847-55
references.pmid: 16687435
references.citation: Cell Mol Biol Lett. 2002;7(2A):457-63
references.pmid: 12378250
references.citation: DNA Repair (Amst). 2006 Jan 5;5(1):1-12
references.pmid: 16202663
references.citation: J Evol Biol. 2006 Jan;19(1):302-8
references.pmid: 16405600
references.citation: Protoplasma. 1997;200(1-2):1-9
references.pmid: 11542471
references.citation: Proc Natl Acad Sci U S A. 2004 May 18;101(20):7624-9
references.pmid: 15123826
references.citation: Neurosci Lett. 2006 Jan 23;393(1):18-22
references.pmid: 16226837
references.citation: Genome. 2006 Nov;49(11):1366-73
references.pmid: 17426751
references.citation: Clin Chem. 1995 Dec;41(12 Pt 2):1854-63
references.pmid: 7497645
references.citation: Mech Ageing Dev. 2003 Aug-Sep;124(8-9):967-75
references.pmid: 14499502
references.citation: Mutat Res. 2006 Mar 20;595(1-2):145-55
references.pmid: 16442571
references.citation: Semin Cancer Biol. 1996 Feb;7(1):15-24
references.pmid: 8695762
references.citation: Plant Physiol. 2006 Jun;141(2):488-97
references.pmid: 16474027
references.citation: Science. 1998 Oct 23;282(5389):662, 679-82
references.pmid: 9784120
references.citation: J Gerontol A Biol Sci Med Sci. 2003 Mar;58(3):205-11
references.pmid: 12634285
references.citation: Trends Plant Sci. 2001 Jun;6(6):248-51
references.pmid: 11378465
references.citation: Plant Physiol. 1970 May;45(5):608-11
references.pmid: 16657353
references.citation: Plant Cell. 2000 Jul;12(7):1093-101
references.pmid: 10899976
references.citation: Nucleic Acids Res. 2003 Feb 1;31(3):974-80
references.pmid: 12560493
references.citation: Rass Int Clin Ter. 1969 Nov 30;49(22):1442-50
references.pmid: 5404853
references.citation: Mech Ageing Dev. 2000 Dec 20;121(1-3):173-9
references.pmid: 11164471
references.citation: Mol Microbiol. 2004 Jun;52(5):1243-53
references.pmid: 15165229
references.citation: J Biol Chem. 1995 Nov 10;270(45):26774-7
references.pmid: 7592914
references.citation: Nucleic Acids Res. 1997 Nov 15;25(22):4650-7
references.pmid: 9358178
references.citation: Nat Rev Genet. 2000 Oct;1(1):40-7
references.pmid: 11262873
references.citation: J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):285-92
references.pmid: 15860462
references.citation: EMBO J. 1987 Dec 20;6(13):3901-7
references.pmid: 3327686
references.citation: J Neurochem. 2002 Mar;80(6):949-59
references.pmid: 11953445
references.citation: J Mol Biol. 2003 Aug 22;331(4):771-9
references.pmid: 12909009
references.citation: Mutat Res. 1997 Jan 31;383(1):61-70
references.pmid: 9042420
references.citation: Plant Cell. 2001 Jan;13(1):61-72
references.pmid: 11158529
references.citation: EMBO J. 2001 May 15;20(10):2587-95
references.pmid: 11350948
references.citation: Mol Gen Genet. 1993 Feb;237(1-2):33-40
references.pmid: 8455565
references.citation: DNA Repair (Amst). 2004 Mar 4;3(3):217-23
references.pmid: 15177037
references.citation: J Neurochem. 2005 Feb;92(4):818-23
references.pmid: 15686483
references.citation: Heredity (Edinb). 2009 Oct;103(4):310-7
references.pmid: 19513093
references.citation: Cell Mol Biol Lett. 2002;7(2A):569-76
references.pmid: 12378262
references.citation: Mol Biol Evol. 2002 Jan;19(1):122-5
references.pmid: 11752198