Christopher E Pearson

Summary

Publications

  1. pmc Repeat associated non-ATG translation initiation: one DNA, two transcripts, seven reading frames, potentially nine toxic entities!
    Christopher E Pearson
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    PLoS Genet 7:e1002018. 2011
  2. doi request reprint Tissue- and age-specific DNA replication patterns at the CTG/CAG-expanded human myotonic dystrophy type 1 locus
    John D Cleary
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    Nat Struct Mol Biol 17:1079-87. 2010
  3. doi request reprint Maternal germline-specific effect of DNA ligase I on CTG/CAG instability
    Stéphanie Tomé
    Program of Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
    Hum Mol Genet 20:2131-43. 2011
  4. pmc Interconverting conformations of slipped-DNA junctions formed by trinucleotide repeats affect repair outcome
    Meghan M Slean
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    Biochemistry 52:773-85. 2013
  5. pmc MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington's disease mice
    Stéphanie Tomé
    Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    PLoS Genet 9:e1003280. 2013
  6. pmc TMPyP4 porphyrin distorts RNA G-quadruplex structures of the disease-associated r(GGGGCC)n repeat of the C9orf72 gene and blocks interaction of RNA-binding proteins
    Bita Zamiri
    From the Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2
    J Biol Chem 289:4653-9. 2014
  7. pmc Replacement of the myotonic dystrophy type 1 CTG repeat with 'non-CTG repeat' insertions in specific tissues
    Michelle M Axford
    Genetics and Genome Biology, The Hospital for Sick Children, TMDT Building 101 College Street, 15th Floor, Rm 15 312 East Tower, Toronto, ON M5G 1L7, Canada
    J Med Genet 48:438-43. 2011
  8. doi request reprint Repeat instability as the basis for human diseases and as a potential target for therapy
    Arturo López Castel
    Program of Genetics and Genome Biology, The Hospital for Sick Children, 101 College Avenue, East Tower 15 312, TMDT Toronto, Ontario, Canada, M5G 1L7
    Nat Rev Mol Cell Biol 11:165-70. 2010
  9. ncbi request reprint Fidelity of primate cell repair of a double-strand break within a (CTG).(CAG) tract. Effect of slipped DNA structures
    Julien L Marcadier
    Department of Molecular and Medical Genetics, University of Toronto, Ontario M5A 1X8, Canada
    J Biol Chem 278:33848-56. 2003
  10. pmc The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni- and multimolecular RNA G-quadruplex structures
    Kaalak Reddy
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada
    J Biol Chem 288:9860-6. 2013

Collaborators

Detail Information

Publications37

  1. pmc Repeat associated non-ATG translation initiation: one DNA, two transcripts, seven reading frames, potentially nine toxic entities!
    Christopher E Pearson
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    PLoS Genet 7:e1002018. 2011
    ..Moreover, since RAN-translation counters the canonical requirements of translation initiation, many new questions are now posed that must be addressed. This review covers RAN-translation and some of the pertinent questions...
  2. doi request reprint Tissue- and age-specific DNA replication patterns at the CTG/CAG-expanded human myotonic dystrophy type 1 locus
    John D Cleary
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    Nat Struct Mol Biol 17:1079-87. 2010
    ..CTCF sites between progressing forks and repeats reduced replication depending on chromatin. Thus, varying replication progression may affect tissue- and age-specific repeat instability...
  3. doi request reprint Maternal germline-specific effect of DNA ligase I on CTG/CAG instability
    Stéphanie Tomé
    Program of Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
    Hum Mol Genet 20:2131-43. 2011
    ..Thus, unlike other DNA metabolizing enzymes studied to date, LigI has a highly specific role in CTG repeat maintenance in the maternal germline, involved in mediating CTG expansions and in the avoidance of maternal CTG contractions...
  4. pmc Interconverting conformations of slipped-DNA junctions formed by trinucleotide repeats affect repair outcome
    Meghan M Slean
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    Biochemistry 52:773-85. 2013
    ..Thus, slipped-junction structure can determine whether repair attempts lead to correction or expansion mutations...
  5. pmc MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington's disease mice
    Stéphanie Tomé
    Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    PLoS Genet 9:e1003280. 2013
    ....
  6. pmc TMPyP4 porphyrin distorts RNA G-quadruplex structures of the disease-associated r(GGGGCC)n repeat of the C9orf72 gene and blocks interaction of RNA-binding proteins
    Bita Zamiri
    From the Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2
    J Biol Chem 289:4653-9. 2014
    ..Disruption of secondary structure formation of the C9orf72 RNA repeats may be a viable therapeutic avenue, as well as a means to test the role of RNA structure upon RAN translation. ..
  7. pmc Replacement of the myotonic dystrophy type 1 CTG repeat with 'non-CTG repeat' insertions in specific tissues
    Michelle M Axford
    Genetics and Genome Biology, The Hospital for Sick Children, TMDT Building 101 College Street, 15th Floor, Rm 15 312 East Tower, Toronto, ON M5G 1L7, Canada
    J Med Genet 48:438-43. 2011
    ..Similarly, a few de novo somatic CTG expansions have been reported to arise from non-expanded DM1 alleles with 5-37 units, thought to be genetically stable...
  8. doi request reprint Repeat instability as the basis for human diseases and as a potential target for therapy
    Arturo López Castel
    Program of Genetics and Genome Biology, The Hospital for Sick Children, 101 College Avenue, East Tower 15 312, TMDT Toronto, Ontario, Canada, M5G 1L7
    Nat Rev Mol Cell Biol 11:165-70. 2010
    ....
  9. ncbi request reprint Fidelity of primate cell repair of a double-strand break within a (CTG).(CAG) tract. Effect of slipped DNA structures
    Julien L Marcadier
    Department of Molecular and Medical Genetics, University of Toronto, Ontario M5A 1X8, Canada
    J Biol Chem 278:33848-56. 2003
    ..These results suggest the existence of primate nuclease activities that are specific for (CTG).(CAG) repeats and the structures they form...
  10. pmc The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni- and multimolecular RNA G-quadruplex structures
    Kaalak Reddy
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada
    J Biol Chem 288:9860-6. 2013
    ....
  11. pmc Human mismatch repair protein hMutLα is required to repair short slipped-DNAs of trinucleotide repeats
    Gagan B Panigrahi
    Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    J Biol Chem 287:41844-50. 2012
    ..The joint involvement of hMutSβ and hMutLα suggests that repeat instability may be the result of aberrant outcomes of repair attempts...
  12. ncbi request reprint Repeat instability: mechanisms of dynamic mutations
    Christopher E Pearson
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, 15 312, TMDT, 101 College Street, East Tower, Toronto, Ontario M5G 1L7, Canada
    Nat Rev Genet 6:729-42. 2005
    ..They have revealed surprising ways in which metabolic pathways can drive or protect from repeat instability...
  13. pmc Identification of restriction endonucleases sensitive to 5-cytosine methylation at non-CpG sites, including expanded (CAG)n/(CTG)n repeats
    Arturo López Castel
    Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
    Epigenetics 6:416-20. 2011
    ....
  14. pmc Isolated short CTG/CAG DNA slip-outs are repaired efficiently by hMutSbeta, but clustered slip-outs are poorly repaired
    Gagan B Panigrahi
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada M5G 1L7
    Proc Natl Acad Sci U S A 107:12593-8. 2010
    ..Our results extend this interference in repair to neurodegenerative disease-causing mutations in which clustered slip-outs escape proper repair and lead to expansions...
  15. pmc Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats
    Kaalak Reddy
    Program of Genetics and Genome Biology, The Hospital for Sick Children, 101 College Street, East Tower, 15 312 TMDT, Toronto, Ontario M5G 1L7, Canada
    Nucleic Acids Res 39:1749-62. 2011
    ..Since each transcribed disease repeat formed R-loops suggests they may have biological functions...
  16. pmc Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues
    Arturo López Castel
    Genetics and Genome Biology, Department of Pediatrics, The Hospital for Sick Children, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
    Hum Mol Genet 20:1-15. 2011
    ..Thus, in humans, the CpG-free expanded CTG repeat appears to maintain a highly polarized pattern of CpG methylation at the DM1 locus, which varies markedly with age and tissues...
  17. ncbi request reprint Slipped (CTG)*(CAG) repeats can be correctly repaired, escape repair or undergo error-prone repair
    Gagan B Panigrahi
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, 555 University Avenue, Elm Wing 11 135, Toronto, Ontario M5G 1X8, Canada
    Nat Struct Mol Biol 12:654-62. 2005
    ..Differential processing of slipped repeats may explain the differences in mutation patterns between various disease loci or tissues...
  18. doi request reprint Mutagenic roles of DNA "repair" proteins in antibody diversity and disease-associated trinucleotide repeat instability
    Meghan M Slean
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1L7
    DNA Repair (Amst) 7:1135-54. 2008
    ..Here we review and compare the mutagenic role of DNA "repair" proteins in the processes of SHM, CSR and TNR instability...
  19. pmc CpG methylation modifies the genetic stability of cloned repeat sequences
    Kerrie Nichol
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8
    Genome Res 12:1246-56. 2002
    ..In vivo CpG methylation in bacteria may have technical applications for the isolation and stable propagation of DNA sequences that have been recalcitrant to isolation and/or analyses because of their extreme instability...
  20. doi request reprint Tissue-specific mismatch repair protein expression: MSH3 is higher than MSH6 in multiple mouse tissues
    Stéphanie Tomé
    Genetics and Genome Biology, The Hospital for Sick Children, TMDT Building 101 College St, 15th Floor, Room 15 312 East Tower, Toronto, ON, M5G 1L7, Canada
    DNA Repair (Amst) 12:46-52. 2013
    ..The relative MMR protein expression levels may explain the functional and tissue-specific reliance upon the roles of each MMR protein...
  21. ncbi request reprint Replication fork dynamics and dynamic mutations: the fork-shift model of repeat instability
    John D Cleary
    Department of Molecular and Medical Genetics, University of Toronto, The Hospital for Sick Children, Ontario, Canada M5G 1X8
    Trends Genet 21:272-80. 2005
    ..The fork-shift model can explain some of the complex behaviours of repeat instability because it is dynamic and responsive to variations in epigenomic and locus activity...
  22. pmc Detection of slipped-DNAs at the trinucleotide repeats of the myotonic dystrophy type I disease locus in patient tissues
    Michelle M Axford
    Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
    PLoS Genet 9:e1003866. 2013
    ..These findings further our understanding of the processes of mutation and genetic variation...
  23. ncbi request reprint Slipped (CTG).(CAG) repeats of the myotonic dystrophy locus: surface probing with anti-DNA antibodies
    Mandy Tam
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, Room 11 135, 555 University Avenue, Elm Wing, M5G 1X8, Toronto, Ont, Canada
    J Mol Biol 332:585-600. 2003
    ..Such features of the repeats may be recognized by cellular proteins known to bind such structures...
  24. ncbi request reprint Evidence of cis-acting factors in replication-mediated trinucleotide repeat instability in primate cells
    John D Cleary
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, 555 University Avenue, Elm Wing 11 135, Toronto, Ontario M5G 1X8, Canada
    Nat Genet 31:37-46. 2002
    ..Our results might explain the variable amounts of CTG/CAG instability that are observed in different chromosomal contexts...
  25. doi request reprint The ATTCT repeats of spinocerebellar ataxia type 10 display strong nucleosome assembly which is enhanced by repeat interruptions
    Katharine A Hagerman
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8
    Gene 434:29-34. 2009
    ..These differences may contribute to phenotypic variation seen between families having pure and interrupted SCA10 repeats, as well as the overall genetic instability at the SCA10 locus...
  26. pmc Processing of double-R-loops in (CAG)·(CTG) and C9orf72 (GGGGCC)·(GGCCCC) repeats causes instability
    Kaalak Reddy
    Department of Genetics, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, 686 Bay Street, Toronto, Ontario M5G 0A4, Canada Program of Molecular Genetics, University of Toronto, Toronto, Ontario M5G 0A4, Canada
    Nucleic Acids Res 42:10473-87. 2014
    ..These findings provide a mechanistic basis for R-loop-mediated instability at disease-associated repeats. ..
  27. pmc CTG/CAG repeat instability is modulated by the levels of human DNA ligase I and its interaction with proliferating cell nuclear antigen: a distinction between replication and slipped-DNA repair
    Arturo López Castel
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada
    J Biol Chem 284:26631-45. 2009
    ....
  28. pmc Quadruplex formation by both G-rich and C-rich DNA strands of the C9orf72 (GGGGCC)8•(GGCCCC)8 repeat: effect of CpG methylation
    Bita Zamiri
    Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada
    Nucleic Acids Res 43:10055-64. 2015
    ..Our findings suggest that for C-rich sequences interspersed with G-residues, one must consider quadruplex formation and that methylation of quadruplexes may affect epigenetic processes. ..
  29. pmc Role of replication and CpG methylation in fragile X syndrome CGG deletions in primate cells
    Kerrie Nichol Edamura
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    Am J Hum Genet 76:302-11. 2005
    ..Templates with 20 CGG repeats were stable under all circumstances. These results reveal that CGG deletions occur during replication and are sensitive to replication-fork dynamics, tract length, and CpG methylation...
  30. ncbi request reprint In vitro (CTG)*(CAG) expansions and deletions by human cell extracts
    Gagan B Panigrahi
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5A 1X8, Canada
    J Biol Chem 277:13926-34. 2002
    ..These results provide new insights into the orientation of replication effect upon repeat stability. This system will be useful in determining the contribution of specific human proteins to (CTG)*(CAG) expansions...
  31. doi request reprint Disease-associated repeat instability and mismatch repair
    Monika H M Schmidt
    Genetics and Genome Biology, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, 686 Bay St, Toronto, Ontario M5G 0A4, Canada Department of Molecular Genetics, University of Toronto, Medical Sciences Bldg, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    DNA Repair (Amst) 38:117-26. 2016
    ..An increasing grasp of these factors holds prognostic and therapeutic potential. ..
  32. ncbi request reprint Deletion hotspot in the argininosuccinate lyase gene: association with topoisomerase II and DNA polymerase alpha sites
    John Christodoulou
    Program in Genetics and Genomic Biology, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    Hum Mutat 27:1065-71. 2006
    ..These findings suggest that the joint presence of these two enzyme sites represents a DNA sequence context that may favor the occurrence of small deletions...
  33. ncbi request reprint Slipping while sleeping? Trinucleotide repeat expansions in germ cells
    Christopher E Pearson
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, 555 University Avenue, Elm Wing 11 135, Toronto, Ontario, Canada M5G 1X8
    Trends Mol Med 9:490-5. 2003
    ..These results have implications both for research aimed at understanding the transmission of this serious mutation and for developing new therapies for the disease...
  34. pmc Replication inhibitors modulate instability of an expanded trinucleotide repeat at the myotonic dystrophy type 1 disease locus in human cells
    Zhi Yang
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    Am J Hum Genet 73:1092-105. 2003
    ..This is the first report that repeat-length alterations specific to a disease allele can be modulated by exogenously added compounds...
  35. pmc Slipped-strand DNAs formed by long (CAG)*(CTG) repeats: slipped-out repeats and slip-out junctions
    Christopher E Pearson
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, 555 University Avenue, Elm Wing 11 135, Toronto, Ontario M5G 1X8, Canada
    Nucleic Acids Res 30:4534-47. 2002
    ....
  36. doi request reprint RAN translation: fragile X in the running
    Kaalak Reddy
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 1L7, Canada
    Neuron 78:405-8. 2013
    ....