Display options
Cite
Oliveira MT, Pontes CB, Ciesielski GL. Roles of the mitochondrial replisome in mitochondrial DNA deletion formation. Genet Mol Biol. 2020;43(1):e20190069doi: 10.1590/1678-4685-GMB-2019-0069.
Oliveira, M. T., Pontes, C. B., & Ciesielski, G. L. (2020). Roles of the mitochondrial replisome in mitochondrial DNA deletion formation. Genetics and molecular biology, 43(1), e20190069. https://doi.org/10.1590/1678-4685-GMB-2019-0069
Oliveira, Marcos T, et al. "Roles of the mitochondrial replisome in mitochondrial DNA deletion formation." Genetics and molecular biology vol. 43,1 (2020): e20190069. doi: https://doi.org/10.1590/1678-4685-GMB-2019-0069
Oliveira MT, Pontes CB, Ciesielski GL. Roles of the mitochondrial replisome in mitochondrial DNA deletion formation. Genet Mol Biol. 2020 Mar 02;43(1):e20190069. doi: 10.1590/1678-4685-GMB-2019-0069. eCollection 2020. PMID: 32141473; PMCID: PMC7197994.
Copy Download .nbib Format: NLM
Share it on

Genet Mol Biol. 2020 Mar 02;43(1):e20190069. doi: 10.1590/1678-4685-GMB-2019-0069. eCollection 2020.

Roles of the mitochondrial replisome in mitochondrial DNA deletion formation.

Genetics and molecular biology

Marcos T Oliveira, Carolina de Bovi Pontes, Grzegorz L Ciesielski

Affiliations

  1. Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Ciências Agrárias e Veterinárias, Departamento de Tecnologia, Jaboticabal, SP, Brazil.
  2. Department of Chemistry, Auburn University at Montgomery, Montgomery, AL, U.S.A.

PMID: 32141473 PMCID: PMC7197994 DOI: 10.1590/1678-4685-GMB-2019-0069

Abstract

Mitochondrial DNA (mtDNA) deletions are a common cause of human mitochondrial diseases. Mutations in the genes encoding components of the mitochondrial replisome, such as DNA polymerase gamma (Pol γ) and the mtDNA helicase Twinkle, have been associated with the accumulation of such deletions and the development of pathological conditions in humans. Recently, we demonstrated that changes in the level of wild-type Twinkle promote mtDNA deletions, which implies that not only mutations in, but also dysregulation of the stoichiometry between the replisome components is potentially pathogenic. The mechanism(s) by which alterations to the replisome function generate mtDNA deletions is(are) currently under debate. It is commonly accepted that stalling of the replication fork at sites likely to form secondary structures precedes the deletion formation. The secondary structural elements can be bypassed by the replication-slippage mechanism. Otherwise, stalling of the replication fork can generate single- and double-strand breaks, which can be repaired through recombination leading to the elimination of segments between the recombination sites. Here, we discuss aberrances of the replisome in the context of the two debated outcomes, and suggest new mechanistic explanations based on replication restart and template switching that could account for all the deletion types reported for patients.

References

  1. Front Genet. 2015 Apr 09;6:135 - PubMed
  2. Am J Hum Genet. 1996 Sep;59(3):591-602 - PubMed
  3. J Biol Chem. 2014 Aug 29;289(35):24032-42 - PubMed
  4. Annu Rev Biochem. 2010;79:181-211 - PubMed
  5. Mol Biol Cell. 2016 Jan 15;27(2):223-35 - PubMed
  6. Enzymes. 2016;39:255-92 - PubMed
  7. Nucleic Acids Res. 1989 Oct 25;17(20):8117-24 - PubMed
  8. Sci Rep. 2018 Jan 29;8(1):1799 - PubMed
  9. Genet Mol Biol. 2013 Sep;36(3):308-15 - PubMed
  10. J Cell Physiol. 2016 Jan;231(1):3-14 - PubMed
  11. J Mol Biol. 1986 Dec 5;192(3):503-11 - PubMed
  12. Nat Commun. 2018 Mar 23;9(1):1202 - PubMed
  13. Muscle Nerve Suppl. 1995;3:S150-3 - PubMed
  14. J Biol Chem. 2009 Aug 7;284(32):21446-57 - PubMed
  15. PLoS One. 2013;8(3):e59907 - PubMed
  16. Gene. 2019 Mar 10;688:171-181 - PubMed
  17. Arch Neurol. 2003 Sep;60(9):1279-84 - PubMed
  18. J Biol Chem. 2014 Oct 24;289(43):29975-93 - PubMed
  19. Ann Clin Transl Neurol. 2014 Nov;1(11):909-20 - PubMed
  20. Science. 2008 Feb 15;319(5865):958-62 - PubMed
  21. Nat Med. 2004 Dec;10(12):1344-51 - PubMed
  22. Hum Mol Genet. 2009 Mar 15;18(6):1028-36 - PubMed
  23. Trends Ecol Evol. 1989 Jan;4(1):6-11 - PubMed
  24. Nucleic Acids Res. 2014 Jan;42(Database issue):D1261-8 - PubMed
  25. Nature. 2013 May 23;497(7450):458-62 - PubMed
  26. Nucleic Acids Res. 2016 Mar 18;44(5):1989-2006 - PubMed
  27. Hum Mol Genet. 2005 Jul 1;14(13):1775-83 - PubMed
  28. DNA Repair (Amst). 2017 Aug;56:118-128 - PubMed
  29. Biochim Biophys Acta. 2009 May;1787(5):312-9 - PubMed
  30. Mol Cell Biol. 2009 Aug;29(16):4441-54 - PubMed
  31. Hum Mol Genet. 2010 Sep 15;19(18):3516-29 - PubMed
  32. Mitochondrial DNA. 2013 Aug;24(4):420-31 - PubMed
  33. Nat Rev Genet. 2012 Dec;13(12):878-90 - PubMed
  34. Mol Biol Evol. 2008 Dec;25(12):2759-70 - PubMed
  35. Hum Mol Genet. 2011 Aug 1;20(15):3052-66 - PubMed
  36. Mitochondrion. 2016 Sep;30:126-37 - PubMed
  37. Nature. 1989 May 25;339(6222):309-11 - PubMed
  38. J Child Neurol. 2014 Sep;29(9):1216-24 - PubMed
  39. Nat Commun. 2019 Feb 15;10(1):759 - PubMed
  40. Nat Genet. 2008 Mar;40(3):275-9 - PubMed
  41. Ann Neurol. 2018 Jan;83(1):115-130 - PubMed
  42. Methods Mol Biol. 2009;554:15-35 - PubMed
  43. Ann Neurol. 2015 May;77(5):753-9 - PubMed
  44. Nucleic Acids Res. 2012 Sep;40(16):7606-21 - PubMed
  45. Am J Hum Genet. 2008 Jan;82(1):228-35 - PubMed
  46. Hum Mol Genet. 2013 Jun 15;22(12):2411-22 - PubMed
  47. Neuromuscul Disord. 2010 Jul;20(7):429-37 - PubMed
  48. Nat Genet. 2001 Jul;28(3):223-31 - PubMed
  49. Nucleic Acids Res. 1991 Feb 11;19(3):493-6 - PubMed
  50. J Hum Genet. 2011 Oct;56(10):689-94 - PubMed
  51. Nucleic Acids Res. 2004 Jun 04;32(10):3053-64 - PubMed
  52. Biochem J. 1996 Sep 15;318 ( Pt 3):1065-70 - PubMed
  53. J Neurol. 2016 Jan;263(1):179-91 - PubMed
  54. Ann Neurol. 2008 Jan;63(1):35-9 - PubMed
  55. Nucleic Acids Res. 2018 Nov 16;46(20):10771-10781 - PubMed
  56. Sci Rep. 2016 Jul 01;6:28942 - PubMed
  57. Cell Metab. 2017 Jan 10;25(1):57-71 - PubMed
  58. EMBO J. 2004 Jun 16;23(12):2423-9 - PubMed
  59. AMA Arch Ophthalmol. 1958 Aug;60(2):280-9 - PubMed
  60. Mol Cell. 2008 Nov 7;32(3):325-36 - PubMed
  61. Hum Mol Genet. 2009 Jan 15;18(2):328-40 - PubMed
  62. Neurol Genet. 2016 Oct 19;2(6):e113 - PubMed
  63. PLoS One. 2017 Apr 28;12(4):e0176795 - PubMed
  64. Neuromuscul Disord. 2012 Jul;22(7):577-86 - PubMed
  65. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7952-6 - PubMed
  66. Nucleic Acids Res. 2013 Jan 7;41(1):632-8 - PubMed
  67. Nucleic Acids Res. 2009 May;37(8):2539-48 - PubMed
  68. BMC Genomics. 2014 Aug 13;15:677 - PubMed
  69. BBA Clin. 2017 Apr 18;7:147-156 - PubMed
  70. J Biol Chem. 2003 Dec 19;278(51):50961-9 - PubMed
  71. Lancet. 2004 Aug 14-20;364(9434):592-6 - PubMed
  72. Nat Genet. 2013 Feb;45(2):214-9 - PubMed
  73. PLoS One. 2013 May 13;8(5):e62340 - PubMed
  74. Hum Mutat. 2003 Dec;22(6):498-9 - PubMed
  75. Nat Struct Mol Biol. 2011 Jul 03;18(8):950-5 - PubMed
  76. J Biol Chem. 2000 Aug 11;275(32):24818-28 - PubMed
  77. Neurol Genet. 2018 Mar 26;4(2):e230 - PubMed
  78. Hum Mol Genet. 2005 Apr 1;14(7):893-902 - PubMed
  79. Science. 1989 Apr 21;244(4902):346-9 - PubMed
  80. PLoS Comput Biol. 2011 Nov;7(11):e1002287 - PubMed
  81. Brain. 2006 Jul;129(Pt 7):1685-92 - PubMed
  82. PLoS Genet. 2009 May;5(5):e1000475 - PubMed
  83. EMBO J. 2011 Aug 26;30(19):4033-46 - PubMed
  84. Cold Spring Harb Symp Quant Biol. 2000;65:81-91 - PubMed
  85. Hum Mol Genet. 2016 Mar 1;25(5):1031-41 - PubMed
  86. Nat Med. 2013 Sep;19(9):1111-3 - PubMed
  87. Microbiol Mol Biol Rev. 2013 Sep;77(3):476-96 - PubMed
  88. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7370-4 - PubMed
  89. Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R244-52 - PubMed
  90. J Biol Chem. 2010 Jun 18;285(25):18984-90 - PubMed
  91. Trends Genet. 2010 Aug;26(8):340-3 - PubMed
  92. Nature. 1988 Feb 25;331(6158):717-9 - PubMed
  93. Genetics. 2012 Mar;190(3):951-64 - PubMed
  94. Brain. 2006 Jul;129(Pt 7):1674-84 - PubMed
  95. Nat Struct Mol Biol. 2014 Oct;21(10):884-92 - PubMed
  96. Mol Cell. 2017 Feb 2;65(3):527-538.e6 - PubMed
  97. Crit Rev Biochem Mol Biol. 2016;51(1):53-64 - PubMed
  98. Mitochondrion. 2007 Feb-Apr;7(1-2):45-52 - PubMed
  99. Nucleic Acids Res. 1990 Feb 11;18(3):561-7 - PubMed
  100. Microbiol Mol Biol Rev. 2007 Mar;71(1):13-35 - PubMed
  101. Sci Rep. 2018 Aug 3;8(1):11682 - PubMed
  102. J Biol Chem. 2005 Sep 9;280(36):31341-6 - PubMed
  103. Brain. 2004 Oct;127(Pt 10):2153-72 - PubMed
  104. Mutat Res. 2007 Jan 3;614(1-2):24-36 - PubMed
  105. Genes Dev. 2005 Oct 15;19(20):2466-76 - PubMed
  106. Nat Genet. 2008 Dec;40(12):1484-8 - PubMed
  107. Trends Genet. 2004 Sep;20(9):393-8 - PubMed
  108. Arch Neurol. 2006 Jan;63(1):107-11 - PubMed
  109. Neurology. 1997 May;48(5):1244-53 - PubMed
  110. Nucleic Acids Res. 2014 Jan;42(2):952-67 - PubMed
  111. Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):17993-8 - PubMed
  112. Curr Opin Chem Biol. 2011 Oct;15(5):580-6 - PubMed
  113. J Biol Chem. 2011 Nov 25;286(47):40649-58 - PubMed
  114. Nucleic Acids Res. 2015 Dec 2;43(21):10102-13 - PubMed
  115. Nat Genet. 2001 Jul;28(3):211-2 - PubMed
  116. EMBO Mol Med. 2014 Apr;6(4):458-66 - PubMed
  117. Nat Rev Genet. 2005 May;6(5):389-402 - PubMed
  118. J Biol Chem. 1998 Sep 11;273(37):23690-7 - PubMed
  119. Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17687-92 - PubMed
  120. Nat Commun. 2018 Jun 27;9(1):2491 - PubMed
  121. Nucleic Acids Res. 2007;35(10):3238-51 - PubMed
  122. Am J Hum Genet. 2008 Aug;83(2):254-60 - PubMed
  123. Nat Commun. 2018 Apr 30;9(1):1727 - PubMed
  124. Am J Hum Genet. 2006 Sep;79(3):469-80 - PubMed
  125. J Med Genet. 2017 Feb;54(2):73-83 - PubMed
  126. Annu Rev Biochem. 2004;73:293-320 - PubMed
  127. Cell Metab. 2016 Jul 12;24(1):3-4 - PubMed
  128. Hum Reprod. 2018 Jul 1;33(7):1331-1341 - PubMed
  129. Nucleic Acids Res. 2016 May 19;44(9):4200-10 - PubMed
  130. Hum Mol Genet. 2010 Jul 1;19(13):2695-705 - PubMed
  131. J Inherit Metab Dis. 2015 Jul;38(4):629-40 - PubMed
  132. J Pharmacol Exp Ther. 2007 Nov;323(2):636-49 - PubMed
  133. Adv Exp Med Biol. 2016;928:27-45 - PubMed
  134. J Biol Chem. 2001 Oct 19;276(42):38555-62 - PubMed
  135. Ann Neurol. 2000 Aug;48(2):188-93 - PubMed
  136. Cell Metab. 2009 Aug;10(2):131-8 - PubMed
  137. J Biol Chem. 2015 Nov 27;290(48):28697-707 - PubMed
  138. Mitochondrion. 2011 Jul;11(4):630-4 - PubMed
  139. Genes (Basel). 2018 Feb 27;9(3): - PubMed
  140. J Hepatol. 2006 Jul;45(1):108-16 - PubMed
  141. Nucleic Acids Res. 2009 Jul;37(13):4218-26 - PubMed
  142. Genome Biol Evol. 2015 Mar 03;7(4):943-59 - PubMed
  143. PLoS One. 2016 Jan 06;11(1):e0145500 - PubMed
  144. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6116-20 - PubMed
  145. Nat Commun. 2015 Jun 22;6:7303 - PubMed
  146. Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11398-11403 - PubMed
  147. EMBO J. 2001 May 15;20(10):2587-95 - PubMed
  148. J Pathol. 2017 Jan;241(2):236-250 - PubMed
  149. J Mol Biol. 2019 Feb 15;431(4):673-686 - PubMed
  150. Mol Cell. 2013 Nov 21;52(4):541-53 - PubMed
  151. Biochim Biophys Acta. 2010 Feb;1797(2):113-28 - PubMed
  152. Methods Mol Biol. 2007;372:219-32 - PubMed
  153. Sci Rep. 2016 Apr 28;6:25186 - PubMed
  154. Am J Hum Genet. 1991 Mar;48(3):492-501 - PubMed
  155. Neurology. 2003 Apr 22;60(8):1354-6 - PubMed
  156. Brain. 2014 Feb;137(Pt 2):323-34 - PubMed
  157. Nat Rev Neurol. 2019 Jan;15(1):40-52 - PubMed
  158. Nature. 2004 May 27;429(6990):417-23 - PubMed
  159. Nucleic Acids Res. 2018 Apr 6;46(6):3034-3046 - PubMed
  160. Nucleic Acids Res. 2015 Oct 30;43(19):9262-75 - PubMed
  161. Bioessays. 2014 Nov;36(11):1024-31 - PubMed

Publication Types