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Simple Sequence Repeats in 5′ and 3′ Flanking Sequences of Cell Cycle Genes

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Perspectives in Cancer Prevention-Translational Cancer Research

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Abstract

Simple sequence repeats (SSRs) are hypermutable, and this instability leads to many disorders. Perhaps it is because of this reason SSRs are relatively rare in coding sequences. The present study was undertaken to explore SSRs in 5′ and 3′ flanking sequences (FS) of cell cycle genes (checkpoint; regulation; replication, repair, and recombination (RRR); and transition) in humans and eight mammalian orthologues. The present study shows more SSRs in FS of regulation genes compared to other gene groups. However, differences in repeat numbers between different groups of cell cycle genes are not significant. Trinucleotide repeats are generally more in 3′ FS of human cell cycle genes but not in other mammals (with some exceptions). On the other hand, in 5′ FS of cell cycle genes (except human genes), trinucleotide repeats are more in number compared to other repeat types in almost all mammals (with some exceptions). Repeat numbers do not differ significantly from other mammals except human and cow genes. Many repeats in FS of human genes are conserved, including rare repeats like CG/GC. CG motifs are conserved only in 5′ and 3′ FS of regulation genes but GC motifs are conserved in RRR genes. This paper presents characteristics of SSRs occurring in 5′ and 3′ FS of cell cycle genes, which may be potential mutational hotspots that could be used for further exploration of their potential roles in gene regulation or medical investigations.

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Abbreviations

Di:

Dinucleotide

FS:

Flanking sequence(s)

Penta:

Penta-nucleotide

SSRs:

Simple sequence repeats

Tetra:

Tetranucleotide

Tri:

Trinucleotide

References

  • Bacolla A, Wells RD (2009) Non-B DNA conformations as determinants of mutagenesis and human disease. Mol Carcinog 48(4):273–285

    Article  PubMed  CAS  Google Scholar 

  • Chambers GK, MacAvoy ES (2000) Microsatellites: consensus and controversy. Comp Biochem Physiol B Biochem Mol Biol 126(4):455–476

    Article  PubMed  CAS  Google Scholar 

  • Chang DK, Metzgar D, Wills C, Boland CR (2001) Microsatellites in the eukaryotic DNA mismatch repair genes as modulators of evolutionary mutation rate. Genome Res 11(7):1145–1146

    Article  PubMed  CAS  Google Scholar 

  • Choudhary OP, Trivedi S (2010) Microsatellite or simple sequence repeat (SSR) instability depends on repeat characteristics during replication and repair. J Cell Molec Biol 8(2):21–34

    CAS  Google Scholar 

  • Corso G, Velho S, Paredes J, Pedrazzani C, Martins D, Milanezi F, Pascale V, Vindigni C, Pinheiro H, Leite M, Marrelli D, Sousa S, Carneiro F, Oliveira C, Roviello F, Seruca R (2011) Oncogenic mutations in gastric cancer with microsatellite instability. Eur J Cancer 47(3):443–451

    Article  PubMed  CAS  Google Scholar 

  • Csink AK, Henikoff S (1998) Something from nothing: the evolution and utility of satellite repeats. Trends Genet 14(5):200–204

    Article  PubMed  CAS  Google Scholar 

  • Deqin M, Chen Z, Nero C, Patel KP, Daoud EM, Cheng H, Djordjevic B, Broaddus RR, Medeiros LJ, Rashid A, Luthra R (2012) Somatic Deletions of the PolyA Tract in the 3′ Untranslated Region of Epidermal Growth Factor Receptor Are Common in Microsatellite Instability-High Endometrial and Colorectal Carcinomas. Arch Pathol Lab Med 136(5):510–516

    Article  PubMed  Google Scholar 

  • Dere R, Napierala M, Ranum LP, Wells RD (2004) Hairpin structure-forming propensity of the (CCTG.CAGG) tetranucleotide repeats contributes to the genetic instability associated with myotonic dystrophy type 2. J Biol Chem 279(40):41715–41726

    Article  PubMed  CAS  Google Scholar 

  • Dieringer D, Schlotterer C (2003) Two distinct modes of microsatellite mutation processes: evidence from the complete genomic sequences of nine species. Genome Res 13:2242–2251

    Article  PubMed  CAS  Google Scholar 

  • Eckert KA, Hile SE (2009) Every microsatellite is different: Intrinsic DNA features dictate mutagenesis of common microsatellites present in the human genome. Mol Carcinog 48(4):379–388

    Article  PubMed  CAS  Google Scholar 

  • Eisen JA, Hanawalt PC (1999) A phylogenomic study of DNA repair genes, proteins, and processes. Mut Res 435:171–213

    Article  CAS  Google Scholar 

  • Ellegren H (2000) Heterogeneous mutation processes in human microsatellite DNA sequences. Nat Genet 24:400–402

    Article  PubMed  CAS  Google Scholar 

  • Fondon JW 3rd, Garner HR (2004) Molecular origins of rapid and continuous morphological evolution. Proc Natl Acad Sci USA 101(52):18058–18063

    Article  PubMed  CAS  Google Scholar 

  • Galindo CL, McCormick JF, Bubb VJ, Abid Alkadem DH, Li LS, McIver LJ, George AC, Boothman DA, Quinn JP, Skinner MA, Garner HR (2011) A long AAAG repeat allele in the 5′-UTR of the ERR-γ gene is correlated with breast cancer predisposition and drives promoter activity in MCF-7 breast cancer cells. Breast Cancer Res Treat 130(1):41–48

    Article  PubMed  CAS  Google Scholar 

  • Gauthier NP, Larsen ME, Wernersson R, de Lichtenberg U, Jensen LJ, Brunak S, Jensen TS (2008) Cyclebase.org-a comprehensive multi-organism online database of cell-cycle experiments. Nucleic Acids Res 36(Database issue):D854–9

    Google Scholar 

  • Jacob KD, Eckert KA (2007) Escherichia coli DNA polymerase IV contributes to spontaneous mutagenesis at coding sequences but not microsatellite alleles. Mut Res 619(1–2):93–103

    CAS  Google Scholar 

  • Joshi-Tope G, Vastrik I, Gopinath GR, Matthews L, Schmidt E, Gillespie M, D'Eustachio P, Jassal B, Lewis S, Wu G, Birney E, Stein L (2003) The genome knowledgebase: a resource for biologists and bioinformaticists. Cold Spring Harb Symp Quant Biol 68:237–243

    Article  PubMed  CAS  Google Scholar 

  • Kashi Y, King DG (2006) Simple sequence repeats as advantageous mutators in evolution. Trends Genet 22(5):253–259

    Article  PubMed  CAS  Google Scholar 

  • Kelder T, Pico AR, Hanspers K, van Iersel MP, Evelo C, Conklin BR (2009) Mining biological pathways using WikiPathways web services. PLoS One 4(7)

    Google Scholar 

  • Kiliszek A, Kierzek R, Krzyzosiak WJ, Rypniewski W (2011) Crystal structures of CGG RNA repeats with implications for fragile X-associated tremor ataxia syndrome. Nucleic Acids Res 39(16):7308–7315

    Article  PubMed  CAS  Google Scholar 

  • Kruglyak S, Durrett RT, Schug MD, Aquadro CF (1998) Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations. Proc Natl Acad Sci USA 95:10774–10778

    Article  PubMed  CAS  Google Scholar 

  • Lahiri M, Gustafson TL, Majors ER, Freudenreich CH (2004) Expanded CAG repeats activate the DNA damage checkpoint pathway. Mol Cell 15(2):287–293

    Article  PubMed  CAS  Google Scholar 

  • Levinson G, Gutman GA (1987) Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol Biol Evol 4:203–221

    PubMed  CAS  Google Scholar 

  • Li M, Chen SS (2011) The tendency to recreate ancestral CG dinucleotides in the human genome. BMC Evol Biol 11:3

    Article  PubMed  CAS  Google Scholar 

  • Li YC, Korol AB, Fahima T, Beiles A, Nevo E (2002) Microsatellites: genomic distribution, putative functions and mutational mechanisms: a review. Mol Ecol 11(12):2453–2465

    Article  PubMed  CAS  Google Scholar 

  • Li YC, Korol AB, Fahima T, Nevo E (2004) Microsatellites within genes: structure, function, and evolution. Mol Biol Evol 21(6):991–1007

    Article  PubMed  CAS  Google Scholar 

  • Lukusa T, Fryns JP (2008) Human chromosome fragility. Biochim Biophys Acta 1779(1):3–16

    Article  PubMed  CAS  Google Scholar 

  • Mao G, Pan X, Gu L (2008) Evidence that a mutation in the MLH1 3′-untranslated region confers a mutator phenotype and mismatch repair deficiency in patients with relapsed leukemia. J Biol Chem 283(6):3211–3216

    Article  PubMed  CAS  Google Scholar 

  • Matthews L, D'Eustachio P, Gillespie M, Croft D, de Bono B, Gopinath G, Jassal B, Lewis S, Schmidt E, Vastrik I, Wu G, Birney E, Stein L (2007) An introduction to the reactome knowledgebase of human biological pathways and processes. Bioinform Primer NCI/Nat Pathway Interact Datab. doi:10.1038/pid.2007.3

    Google Scholar 

  • Matthews L, Gopinath G, Gillespie M, Caudy M, Croft D, de Bono B, Garapati P, Hemish J, Hermjakob H, Jassal B, Kanapin A, Lewis S, Mahajan S, May B, Schmidt E, Vastrik I, Wu G, Birney E, Stein L, D’Eustachio P (2009) Reactome knowledgebase of biological pathways and processes. Nucleic Acids Res 37(Database issue):D619–D622

    Article  PubMed  CAS  Google Scholar 

  • Metzgar D, Bytof J, Wills C (2000) Selection against frameshift mutations limits microsatellite expansion in coding DNA. Genome Res 10(1):72–80

    PubMed  CAS  Google Scholar 

  • Pavlidis P, Noble WS (2003) Matrix2png: a utility for visualizing matrix data. Bioinformatics 19:295–296. doi:10.1093/bioinformatics/19.2.295

    Article  PubMed  CAS  Google Scholar 

  • Pico AR, Kelder T, van Iersel MP, Hanspers K, Conklin BR, Evelo C (2008) WikiPathways: pathway editing for the people. PLoS Biol 6(7)

    Google Scholar 

  • Ray BK, Dhar S, Shakya A, Ray A (2011) Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression. Proc Natl Acad Sci USA 108(1):103–108

    Article  PubMed  CAS  Google Scholar 

  • Regelson M, Eller CD, Horvath S, Marahrens Y (2006) A link between repetitive sequences and gene replication time. Cytogenet Genome Res 112(3–4):184–193

    Article  PubMed  CAS  Google Scholar 

  • Russell L, Forsdyke DR (1991) A human putative lymphocyte G0/G1 switch gene containing a CpG-rich island encodes a small basic protein with the potential to be phosphorylated. DNA Cell Biol 10(8):581–591

    Article  PubMed  CAS  Google Scholar 

  • Shin J, Yuan Z, Fordyce K, Sreeramoju P, Kent TS, Kim J, Wang V, Schneyer D, Weber TK (2007) A del T poly T (8) mutation in the 3′ untranslated region (UTR) of the CDK2-AP1 gene is functionally significant causing decreased mRNA stability resulting in decreased CDK2-AP1 expression in human microsatellite unstable (MSI) colorectal cancer (CRC). Surgery 142(2):222–227

    Article  PubMed  Google Scholar 

  • Strand M, Prolla TA, Liskay RM, Petes TD (1993) Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365:274–276

    Article  PubMed  CAS  Google Scholar 

  • Sugiyama M, Tanaka Y, Wakita T, Nakanishi M, Mizokami M (2011) Genetic variation of the IL-28B promoter affecting gene expression. PLoS One 6(10):e26620

    Article  PubMed  CAS  Google Scholar 

  • The Gene Ontology Consortium (2000) Gene Ontology: tool for the unification of biology. Nature Genet 25:25–29. http://amigo.geneontology.org/cgi-bin/amigo/browse.cgi

    Google Scholar 

  • Tian X, Strassmann JE, Queller DC (2011) Genome nucleotide composition shapes variation in simple sequence repeats. Mol Biol Evol 28(2):899–909

    Article  PubMed  CAS  Google Scholar 

  • Toth G, Gaspari Z, Jurka J (2000) Microsatellites in different eukaryotic genomes: survey and analysis. Genome Res 10:967–981

    Article  PubMed  CAS  Google Scholar 

  • Tripathi Bhar A, Banerjee S, Chunder N, Roy A, Sengupta A, Roy B, Roychowdhury S, Panda CK (2003) Differential alterations of the genes in the CDKN2A-CCND1-CDK4-RB1 pathway are associated with the development of head and neck squamous cell carcinoma in Indian patients. J Cancer Res Clin Oncol 129(11):642–650

    Article  PubMed  Google Scholar 

  • Trivedi S (2003) Do microsatellites have biased associations? Nucleus 46:61–76

    Google Scholar 

  • Trivedi S (2006) Comparison of simple sequence repeats in 19 Archaea. Genet Mol Res 5(4):741–772

    PubMed  CAS  Google Scholar 

  • Trivedi S (2010) Do simple sequence repeats in replication, repair and recombination genes of mycoplasmas provide genetic variability? J Cell Mole Biol 7(2) & 7(2 & 8(1)):53–70

    Google Scholar 

  • Va Vastrik I, D'Eustachio P, Schmidt E, Joshi-Tope G, Gopinath G, Croft D, de Bono B, Gillespie M, Jassal B, Lewis S, Matthews L, Wu G, Birney E, Stein L (2007) Reactome: a knowledge base of biologic pathways and processes. Genome Biol 8:R39

    Article  Google Scholar 

  • Wang L, Lin S, Rammohan KW, Liu Z, Liu JQ, Liu RH, Guinther N, Lima J, Zhou Q, Wang T, Zheng X, Birmingham DJ, Rovin BH, Hebert LA, Wu Y, Lynn DJ, Cooke G, Yu CY, Zheng P, Liu Y (2007) A dinucleotide deletion in CD24 confers protection against autoimmune diseases. PLoS Genet 3(4):e49

    Article  PubMed  Google Scholar 

  • Xu X, Peng M, Fang Z (2000) The direction of microsatellite mutations is dependent upon allele length. Nat Genet 24:396–399

    Article  PubMed  CAS  Google Scholar 

  • Yuan Z, Shin J, Wilson A, Goel S, Ling YH, Ahmed N, Dopeso H, Jhawer M, Nasser S, Montagna C, Fordyce K, Augenlicht LH, Aaltonen LA, Arango D, Weber TK, Mariadason JM (2009) An A13 repeat within the 3′-untranslated region of epidermal growth factor receptor (EGFR) is frequently mutated in microsatellite instability colon cancers and is associated with increased EGFR expression. Cancer Res 69(19):7811–7818

    Article  PubMed  CAS  Google Scholar 

  • Zahra R, Blackwood JK, Sales J, Leach DR (2007) Proofreading and secondary structure processing determine the orientation dependence of CAG × CTG trinucleotide repeat instability in Escherichia coli. Genetics 176(1):27–41

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

I am grateful to Mr. Abhay Pendse for help with computational work. I am indebted to Ensembl workgroup especially Dr. Javier Herrero (Ensembl Compara Project Leader, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK) for their help in obtaining multiple aligned sequences. Further, I am obliged to all open-source journals, databases, and scientists who provided reprints and information related to this work.

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Authors and Affiliations

  1. Department of Zoology, JN Vyas University, Jodhpur, Rajasthan, 342011, India

    Seema Trivedi

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  1. Seema Trivedi
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Correspondence to Seema Trivedi .

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Editors and Affiliations

  1. Computational Biology & Bioinformatics, University of Kerala, Kariavattom, Trivandrum, Kerala, India

    Perumana R. Sudhakaran

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Trivedi, S. (2014). Simple Sequence Repeats in 5′ and 3′ Flanking Sequences of Cell Cycle Genes. In: R. Sudhakaran, P. (eds) Perspectives in Cancer Prevention-Translational Cancer Research. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1533-2_7

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