Match!

R-loops: targets for nuclease cleavage and repeat instability

Published on Aug 1, 2018in Current Genetics3.46
· DOI :10.1007/s00294-018-0806-z
Catherine H. Freudenreich23
Estimated H-index: 23
(Tufts University)
Abstract
R-loops form when transcribed RNA remains bound to its DNA template to form a stable RNA:DNA hybrid. Stable R-loops form when the RNA is purine-rich, and are further stabilized by DNA secondary structures on the non-template strand. Interestingly, many expandable and disease-causing repeat sequences form stable R-loops, and R-loops can contribute to repeat instability. Repeat expansions are responsible for multiple neurodegenerative diseases, including Huntington’s disease, myotonic dystrophy, and several types of ataxias. Recently, it was found that R-loops at an expanded CAG/CTG repeat tract cause DNA breaks as well as repeat instability (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392–E8401, 2017). Two factors were identified as causing R-loop-dependent breaks at CAG/CTG tracts: deamination of cytosines and the MutLγ (Mlh1–Mlh3) endonuclease, defining two new mechanisms for how R-loops can generate DNA breaks (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392–E8401, 2017). Following R-loop-dependent nicking, base excision repair resulted in repeat instability. These results have implications for human repeat expansion diseases and provide a paradigm for how RNA:DNA hybrids can cause genome instability at structure-forming DNA sequences. This perspective summarizes mechanisms of R-loop-induced fragility at G-rich repeats and new links between DNA breaks and repeat instability.
  • References (62)
  • Citations (14)
References62
Newest
#1Ryan J. McGinty (Tufts University)H-Index: 4
#2Rachel G. Rubinstein (Tufts University)H-Index: 1
Last.Sergei M. Mirkin (Tufts University)H-Index: 40
view all 7 authors...
11 CitationsSource
16 CitationsSource
#1Jong-Min Lee (Broad Institute)H-Index: 19
#2Michael J. Chao (Harvard University)H-Index: 6
Last.James F. Gusella (Broad Institute)H-Index: 116
view all 13 authors...
16 CitationsSource
#1Norma Keogh (National University of Ireland, Galway)H-Index: 1
#2Kara Y. Chan (UK: University of Kentucky)H-Index: 1
Last.Robert S. Lahue (National University of Ireland, Galway)H-Index: 26
view all 4 authors...
5 CitationsSource
#1Davina J. Hensman Moss (UCL: University College London)H-Index: 6
#2Antonio F. Pardiñas (Cardiff University)H-Index: 12
Last.Peter Holmans (Cardiff University)H-Index: 94
view all 735 authors...
59 CitationsSource
#1Ryan J. McGinty (Tufts University)H-Index: 4
#2Franco Puleo (Tufts University)H-Index: 1
Last.Sergei M. Mirkin (Tufts University)H-Index: 40
view all 10 authors...
4 CitationsSource
#1Qiao-Hua Qiao (Harvard University)H-Index: 9
#2Li Wang (Harvard University)H-Index: 4
Last.Hao Wu (Harvard University)H-Index: 82
view all 6 authors...
35 CitationsSource
#1Erica J. Polleys (Tufts University)H-Index: 3
#2Nealia C.M. House (Tufts University)H-Index: 5
Last.Catherine H. Freudenreich (Tufts University)H-Index: 23
view all 3 authors...
16 CitationsSource
#1Aris Polyzos (LBNL: Lawrence Berkeley National Laboratory)H-Index: 10
#2Cynthia T. McMurray (LBNL: Lawrence Berkeley National Laboratory)H-Index: 11
13 CitationsSource
#1Carol M. Manhart (Cornell University)H-Index: 5
#2Xiaodan Ni (McMaster University)H-Index: 3
Last.Eric Alani (Cornell University)H-Index: 44
view all 6 authors...
17 CitationsSource
Cited By14
Newest
#1Cinzia Cinesi (UNIL: University of Lausanne)H-Index: 1
#2Bin Yang (UNIL: University of Lausanne)H-Index: 1
Last.Vincent Dion (Cardiff University)
view all 3 authors...
Source
#1Kamila K. Myka (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 1
#2Max E. Gottesman (CUMC: Columbia University Medical Center)H-Index: 52
1 CitationsSource
#1Nadine Puget (University of Toulouse)H-Index: 6
#2Kyle M. Miller (University of Texas at Austin)H-Index: 26
Last.Gaëlle Legube (University of Toulouse)H-Index: 26
view all 3 authors...
1 CitationsSource
#1Valentina Infantino (University of Geneva)H-Index: 1
#2Françoise Stutz (University of Geneva)H-Index: 34
Source
#1Lindsey D. Goodman (UPenn: University of Pennsylvania)H-Index: 5
#2Mercedes Prudencio (Mayo Clinic)H-Index: 19
Last.Nancy M. Bonini (UPenn: University of Pennsylvania)H-Index: 56
view all 14 authors...
3 CitationsSource
#1Martina G. L. Perego (University of Milan)H-Index: 1
#2Michela Taiana (University of Milan)H-Index: 6
Last.Stefania Corti (University of Milan)H-Index: 44
view all 5 authors...
4 CitationsSource
#1Norah Owiti (MIT: Massachusetts Institute of Technology)H-Index: 1
#2Kasey Stokdyk (University of Texas Health Science Center at Houston)H-Index: 1
Last.Nayun Kim (University of Texas Health Science Center at Houston)H-Index: 1
view all 3 authors...
1 CitationsSource
#1Yanhao Lai (FIU: Florida International University)
#2Ruipeng Lei (FIU: Florida International University)
Last.Yuan Liu (FIU: Florida International University)H-Index: 13
view all 4 authors...
Source
#1Mauno Vihinen (Lund University)H-Index: 56
Source
Last.Vibe H. OestergaardH-Index: 12
view all 3 authors...
1 CitationsSource