FRED PERRINO

Summary

Affiliation: Wake Forest University School of Medicine
Country: USA

Publications

  1. ncbi request reprint Two functional domains of the epsilon subunit of DNA polymerase III
    F W Perrino
    Wake Forest University School of Medicine, Department of Biochemistry, Winston Salem, North Carolina 27157, USA
    Biochemistry 38:16001-9. 1999
  2. pmc RNaseH2 mutants that cause Aicardi-Goutieres syndrome are active nucleases
    Fred W Perrino
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC, 27157, USA
    J Mol Med (Berl) 87:25-30. 2009
  3. pmc Cooperative DNA binding and communication across the dimer interface in the TREX2 3' --> 5'-exonuclease
    Fred W Perrino
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
    J Biol Chem 283:21441-52. 2008
  4. ncbi request reprint Polymerization past the N2-isopropylguanine and the N6-isopropyladenine DNA lesions with the translesion synthesis DNA polymerases eta and iota and the replicative DNA polymerase alpha
    Fred W Perrino
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    Chem Res Toxicol 18:1451-61. 2005
  5. ncbi request reprint The human TREX2 3' -> 5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis
    Fred W Perrino
    Department of Biochemistry, Center for Structural Biology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    J Biol Chem 280:15212-8. 2005
  6. pmc DNA binding induces active site conformational change in the human TREX2 3'-exonuclease
    Udesh de Silva
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
    Nucleic Acids Res 37:2411-7. 2009
  7. pmc Lesion bypass of N2-ethylguanine by human DNA polymerase iota
    Matthew G Pence
    Department of Biochemistry and Center for Structural Biology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    J Biol Chem 284:1732-40. 2009
  8. ncbi request reprint The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partnering
    Udesh de Silva
    Department of Biochemistry, Center for Structural Biology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157
    J Biol Chem 282:10537-43. 2007
  9. pmc The structure of the mammalian RNase H2 complex provides insight into RNA.NA hybrid processing to prevent immune dysfunction
    Nadine M Shaban
    Department of Biochemistry, Center for Structural Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 285:3617-24. 2010
  10. ncbi request reprint Sequence variants in the 3'-->5' deoxyribonuclease TREX2: identification in a genetic screen and effects on catalysis by the recombinant proteins
    Fred W Perrino
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
    Adv Enzyme Regul 44:37-49. 2004

Research Grants

  1. Mechanisms of the 3'-->5' deoxyribonucleases
    Fred W Perrino; Fiscal Year: 2010
  2. Mechanisms of the 3'-->5' deoxyribonucleases
    FRED PERRINO; Fiscal Year: 2009
  3. Mechanisms of the 3'-5' deoxyribonucleases
    FRED PERRINO; Fiscal Year: 2007
  4. Mechanisms of the 3'-->5' deoxyribonucleases
    FRED PERRINO; Fiscal Year: 2009

Collaborators

  • David Horita
  • R E London
  • Min Ae Lee Kirsch
  • Vilhelm A Bohr
  • Torsten Witte
  • D M Wilson
  • BRUCE F DEMPLE
  • Deborah E Barnes
  • Yanick J Crow
  • Scott Harvey
  • Thomas Hollis
  • Udesh de Silva
  • Min Ae Lee-Kirsch
  • Dipanjan Chowdhury
  • Eugene F Derose
  • Dana C Upton
  • Duane A Lehtinen
  • James C Fishbein
  • Patrick Blans
  • Judy Lieberman
  • Roel M Schaaper
  • Nadine M Shaban
  • Matthew G Pence
  • Suzanna L Bailey
  • Kerstin Engel
  • Lydia Senenko
  • Christiane Pfeiffer
  • Gillian Rice
  • Manfred Gahr
  • Norbert Hubner
  • Jeanine A Harrigan
  • Xueying Wang
  • Steven A Akman
  • Thomas W Kirby
  • Thomas Darden
  • Charles N Zink
  • Matthew J Mulcahy
  • Andrew P Bowden
  • Ariane L Herrick
  • Reinhold E Schmidt
  • Rekha Parmar
  • Teresa Patrick
  • Maoliang Gong
  • Young Ae Lee
  • Peter Robins
  • Timothy J Vyse
  • Tomas Lindahl
  • Oliver Hummel
  • Juha Kere
  • Sumana Choudhury
  • Klaus Rohde
  • William G Newman
  • Jamil Momand
  • John Dean
  • Ann O'Hara
  • Jinshui Fan
  • Maolian Gong
  • Sari Koskenmies
  • Andrew Wong
  • Kim Flintoff
  • Anna F Dominiczak
  • Sergey Chalov
  • Paul J Beresford
  • Lars C Pedersen
  • Anna K Chikova
  • Jung Suk Sung
  • Dong Zhang
  • Pengcheng Zhu
  • Scott Gabel
  • Dawei Li

Detail Information

Publications23

  1. ncbi request reprint Two functional domains of the epsilon subunit of DNA polymerase III
    F W Perrino
    Wake Forest University School of Medicine, Department of Biochemistry, Winston Salem, North Carolina 27157, USA
    Biochemistry 38:16001-9. 1999
    ..These data support the concept that epsilon contains a catalytic domain located within the N-terminal region and an alpha-association domain located within the C-terminal region of the protein...
  2. pmc RNaseH2 mutants that cause Aicardi-Goutieres syndrome are active nucleases
    Fred W Perrino
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC, 27157, USA
    J Mol Med (Berl) 87:25-30. 2009
    ....
  3. pmc Cooperative DNA binding and communication across the dimer interface in the TREX2 3' --> 5'-exonuclease
    Fred W Perrino
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
    J Biol Chem 283:21441-52. 2008
    ..A DNA binding analysis of TREX2 and the heterodimers indicates a cooperative binding effect within the TREX2 protomer. Finally, single turnover kinetic assays identify DNA binding as the rate-limiting step in TREX2 catalysis...
  4. ncbi request reprint Polymerization past the N2-isopropylguanine and the N6-isopropyladenine DNA lesions with the translesion synthesis DNA polymerases eta and iota and the replicative DNA polymerase alpha
    Fred W Perrino
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    Chem Res Toxicol 18:1451-61. 2005
    ....
  5. ncbi request reprint The human TREX2 3' -> 5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis
    Fred W Perrino
    Department of Biochemistry, Center for Structural Biology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    J Biol Chem 280:15212-8. 2005
    ....
  6. pmc DNA binding induces active site conformational change in the human TREX2 3'-exonuclease
    Udesh de Silva
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
    Nucleic Acids Res 37:2411-7. 2009
    ..The structure also shows how TREX proteins potentially interact with double-stranded DNA and suggest features that might be involved in strand denaturation to provide a single-stranded substrate for the active site...
  7. pmc Lesion bypass of N2-ethylguanine by human DNA polymerase iota
    Matthew G Pence
    Department of Biochemistry and Center for Structural Biology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    J Biol Chem 284:1732-40. 2009
    ....
  8. ncbi request reprint The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partnering
    Udesh de Silva
    Department of Biochemistry, Center for Structural Biology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157
    J Biol Chem 282:10537-43. 2007
    ..The structure also reveals an 8-amino acid polyproline II helix within the TREX1 enzyme that suggests a mechanism for interactions of this exonuclease with other protein complexes...
  9. pmc The structure of the mammalian RNase H2 complex provides insight into RNA.NA hybrid processing to prevent immune dysfunction
    Nadine M Shaban
    Department of Biochemistry, Center for Structural Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 285:3617-24. 2010
    ....
  10. ncbi request reprint Sequence variants in the 3'-->5' deoxyribonuclease TREX2: identification in a genetic screen and effects on catalysis by the recombinant proteins
    Fred W Perrino
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
    Adv Enzyme Regul 44:37-49. 2004
  11. ncbi request reprint The N2-ethylguanine and the O6-ethyl- and O6-methylguanine lesions in DNA: contrasting responses from the "bypass" DNA polymerase eta and the replicative DNA polymerase alpha
    Fred W Perrino
    Department of Biochemistry and Department of Cancer Biology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    Chem Res Toxicol 16:1616-23. 2003
    ..These results suggest that accurate replication past the N(2)-ethylGua adduct might be facilitated in cells by pausing of replication catalyzed by DNA polymerase alpha and lesion bypass catalyzed by DNA polymerase eta...
  12. pmc The TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease
    Duane A Lehtinen
    Department of Biochemistry, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    J Biol Chem 283:31649-56. 2008
    ..The dysfunctional dsDNA degradation activities of these disease-related TREX1 mutants could account for persistent dsDNA from dying cells leading to an aberrant immune response in these clinically related disorders...
  13. pmc Dysfunctional proofreading in the Escherichia coli DNA polymerase III core
    Duane A Lehtinen
    Wake Forest University Health Sciences, Department of Biochemistry, Winston Salem, NC 27157, USA
    Biochem J 384:337-48. 2004
    ..Thus the epsilon511 mutant has wild-type 3'-->5' exonuclease activity and associates physically with the alpha- and theta;-subunits to generate a proofreading-defective DNA pol III enzyme...
  14. ncbi request reprint Mutagenesis by exocyclic alkylamino purine adducts in Escherichia coli
    Dana C Upton
    Wake Forest University Health Sciences, Winston Salem, NC, USA
    Mutat Res 599:1-10. 2006
    ..We conclude that N(2)-ethyl and -isopropyldeoxyguanosine are mutagenic adducts in E. coli whose mutation spectra differ markedly from that of O(6)-ethyldeoxyguanosine...
  15. ncbi request reprint The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death
    Dipanjan Chowdhury
    CBR Institute for Biomedical Research, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 23:133-42. 2006
    ..After granzyme A activates NM23-H1 to make single-stranded nicks, TREX1 removes nucleotides from the nicked 3' end to reduce the possibility of repair by rejoining the nicked ends...
  16. ncbi request reprint Model for the catalytic domain of the proofreading epsilon subunit of Escherichia coli DNA polymerase III based on NMR structural data
    Eugene F Derose
    Laboratory of Structural Biology and Laboratory of Molecular Genetics, NIEHS, Box 12233, Research Triangle Park, North Carolina 27709, USA
    Biochemistry 41:94-110. 2002
    ..Nearly all of the residues which have been identified as mutators are located in the portion of the molecule which binds the DNA, with most of these playing either a catalytic or structural role...
  17. ncbi request reprint Elucidation of the epsilon-theta subunit interface of Escherichia coli DNA polymerase III by NMR spectroscopy
    Eugene F Derose
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Box 12233, Research Triangle Park, North Carolina 27709, USA
    Biochemistry 42:3635-44. 2003
    ..These chemical shift mapping results also suggest an explanation for how the unstable dnaQ49 mutator phenotype of epsilon may be stabilized by binding theta...
  18. pmc Structure of the Escherichia coli DNA polymerase III epsilon-HOT proofreading complex
    Thomas W Kirby
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences NIH, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA
    J Biol Chem 281:38466-71. 2006
    ..This structure provides insight into how HOT and, by implication, may stabilize the epsilon subunit, thus promoting efficient proofreading during chromosomal replication...
  19. ncbi request reprint A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus
    Min Ae Lee-Kirsch
    Klinik fur Kinder und Jugendmedizin, Technische Universitat Dresden, Fetscherstr 74, 01307, Dresden, Germany
    J Mol Med (Berl) 85:531-7. 2007
    ..Our findings also warrant further investigation of TREX1 in common forms of lupus erythematosus...
  20. pmc Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome
    Gillian Rice
    Leeds Institute of Molecular Medicine, St James s University Hospital, Leeds, LS9 7TF, UK
    Am J Hum Genet 80:811-5. 2007
    ..Additionally, we describe a de novo heterozygous mutation, affecting a critical catalytic residue in TREX1, that results in typical Aicardi-Goutieres syndrome...
  21. pmc WRN exonuclease activity is blocked by DNA termini harboring 3' obstructive groups
    Jeanine A Harrigan
    Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States
    Mech Ageing Dev 128:259-66. 2007
    ....
  22. ncbi request reprint Replication of N2-ethyldeoxyguanosine DNA adducts in the human embryonic kidney cell line 293
    Dana C Upton
    Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    Chem Res Toxicol 19:960-7. 2006
    ..Taken together, these data indicate that N(2)-ethyldGuo in DNA exerts its principal biological activity by blocking translesion DNA synthesis in human cells, resulting in either failure of replication or frameshift deletion mutations...
  23. ncbi request reprint Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus
    Min Ae Lee-Kirsch
    Klinik fur Kinder und Jugendmedizin, Technische Universitat Dresden, 01307 Dresden, Germany
    Nat Genet 39:1065-7. 2007
    ..1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE...

Research Grants11

  1. Mechanisms of the 3'-->5' deoxyribonucleases
    Fred W Perrino; Fiscal Year: 2010
    ..The outcome of the proposed research will have a significant impact on the medical treatment of complex autoimmune diseases such as systemic lupus erythematosus. ..
  2. Mechanisms of the 3'-->5' deoxyribonucleases
    FRED PERRINO; Fiscal Year: 2009
    ..The outcome of the proposed research will have a significant impact on the medical treatment of complex autoimmune diseases such as systemic lupus erythematosus. ..
  3. Mechanisms of the 3'-5' deoxyribonucleases
    FRED PERRINO; Fiscal Year: 2007
    ..Identification of the TREX genes encoding these 3'-->5' deoxyribonucleases has made possible these mechanistic studies that will provide new insights into the physiological function of these enzymes. ..
  4. Mechanisms of the 3'-->5' deoxyribonucleases
    FRED PERRINO; Fiscal Year: 2009
    ..The outcome of the proposed research will have a significant impact on the medical treatment of complex autoimmune diseases such as systemic lupus erythematosus. ..