MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, Dec. 2008, p. 686–727 Vol. 72, No. 4 1092-2172/08/$08.00ϩ0 doi:10.1128/MMBR.00011-08 Copyright © 2008, American Society for Microbiology. All Rights Reserved. Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes Guy-Franck Richard,* Alix Kerrest, and Bernard Dujon Institut Pasteur, Unite´deGe´ne´tique Mole´culaire des Levures, CNRS, URA2171, Universite´Pierre et Marie Curie, UFR927, 25 rue du Dr. Roux, F-75015, Paris, France INTRODUCTION .......................................................................................................................................................687 From Biophysics to Whole-Genome Sequencing ................................................................................................687 REPEATED DNA SEQUENCES IN EUKARYOTIC GENOMES.......................................................................688 Whole-Genome Duplications and Segmental Duplications ..............................................................................688 Whole-genome and segmental duplications in hemiascomycetes.................................................................688 Whole-genome and segmental duplications in vertebrates...........................................................................689 Whole-genome and segmental duplications in angiosperms ........................................................................689 Whole-genome duplications in Paramecium....................................................................................................690 Dispersed DNA Repeats.........................................................................................................................................690 Paralogous genes and gene families.................................................................................................................690 Genes encoding tRNA: tDNA ............................................................................................................................691 Transposable elements.......................................................................................................................................691 (i) LINEs..........................................................................................................................................................692 (ii) SINEs.........................................................................................................................................................692 (iii) LTR retroelements and retroviruses....................................................................................................692 (iv) DNA transposons.....................................................................................................................................693 (v) Inactivation of repeated elements in fungi ...........................................................................................693 Tandem DNA Repeats............................................................................................................................................693 Tandem repeats of paralogues..........................................................................................................................694 rDNA repeated arrays ........................................................................................................................................694 Satellite DNA.......................................................................................................................................................695 Microsatellites and minisatellites.....................................................................................................................696 (i) Distribution of microsatellites in eukaryotic genomes.........................................................................697 (ii) Distribution of minisatellites in eukaryotic genomes .........................................................................698 (iii) Alu elements and microsatellites ..........................................................................................................699 MINI- AND MICROSATELLITE SIZE CHANGES: FROM HUMAN DISORDERS TO SPECIATION.....699 Fragile Sites and Cancer .......................................................................................................................................699 DNA repeats found at fragile sites...................................................................................................................700 Molecular basis for fragility..............................................................................................................................700 Fragile sites and chromosomal rearrangements in cancers .........................................................................701 Trinucleotide Repeat Expansions .........................................................................................................................701 Trinucleotide repeat expansions in noncoding sequences ............................................................................702 Trinucleotide repeat expansions in coding sequences...................................................................................702 (i) Polyglutamine expansions ........................................................................................................................702 (ii) Polyalanine expansions ...........................................................................................................................703 The timing of expansions...................................................................................................................................703 Micro- and Minisatellite Size Polymorphism: an Evolutionary Driving Force .............................................703 Evolution of FLO genes in Saccharomyces cerevisiae......................................................................................703 Roles of microsatellites in vertebrate evolution .............................................................................................704 Molecular Mechanisms Involved in Mini- and Microsatellite Expansions....................................................704 DNA secondary structures are involved in microsatellite instability..........................................................704 Chromatin assembly is modified by trinucleotide repeats............................................................................706 DNA replication of mini- and microsatellites.................................................................................................706 (i) Effect of DNA replication on microsatellites.........................................................................................706 (ii) Effect of DNA replication on minisatellites..........................................................................................708 (iii) cis-acting effects: repeat location, purity, and orientation ................................................................708 (iv) Replication fork stalling and fork reversal..........................................................................................709 * Corresponding author. Mailing address: Institut Pasteur, Unite´de Ge´ne´tique Mole´culaire des Levures, CNRS, URA2171, Universite´ Pierre et Marie Curie, UFR927, 25 rue du Dr. Roux, F-75015, Paris, France. Phone: (33)-1-40-61-34-54. Fax: (33)-1-40-61-34-56. E-mail: [email protected]. 686 VOL. 72, 2008 DNA REPEATS IN EUKARYOTES 687 (v) Effect of DNA damage checkpoints on trinucleotide repeat instability ............................................710 Defects in mismatch repair dramatically increase microsatellite instability .......................................................710 Role of the error-free postreplication repair pathway on trinucleotide repeat expansions.....................711 Mini- and microsatellite rearrangements during homologous recombination ..........................................711 (i) Expansions and contractions during meiotic recombination..............................................................712 (ii) Expansions and contractions during mitotic recombination.............................................................713 Revisiting the trinucleotide repeat expansion model.....................................................................................714 PERSPECTIVES: REPEATED QUESTIONS AND NEW CHALLENGES........................................................715 Going from One to Two: Birth and Death of Microsatellites ..........................................................................715 Toward a Unique Definition of Micro- and Minisatellites ...............................................................................715 A Final Word...........................................................................................................................................................715 ACKNOWLEDGMENTS ...........................................................................................................................................716 REFERENCES ............................................................................................................................................................716 INTRODUCTION content of the unicellular amoeba Amoeba dubia was 200 times higher than that in humans. This was called the “C-value par- At the dawn of the 21st century, the human genome was adox”