R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde
Abstract
:1. Introduction
2. Dual Nature of R-Loops
3. R-Loops Accumulation: Why and Where
4. Prevention Mechanisms to Avoid R-Loop Accumulation
5. Resolving Mechanisms to Remove R-Loops
6. The Enigmatic Role of RNA:DNA Hybrids in DNA Repair
7. Role of Epigenetic Marks in R-Loop Homeostasis
8. The Role of the Chro-Mates Part I: Chromatin Modifiers
8.1. EHMT2/G9a
8.2. SIRT6
8.3. SIRT7
8.4. Sin3A
8.5. RNF168
9. The Role of the Chro-Mates Part II: Chromatin Remodelers
9.1. MDM2
9.2. ATRX
9.3. FACT/SETD2
9.4. INO80
9.5. BRG1
9.6. Fft3/SMARCAD1
10. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
53BP1 | p53 Binding Protein 1 |
AGS | Aicardi-Goutières Syndrome |
AID | Activation-Induced Deaminase |
ALS4 | Amyotrophic Lateral Sclerosis type 4 |
ALT | Alternative Lengthening of Telomeres |
AOA2 | Ataxia with Oculomotor Apraxia type 2 |
ASF1 | Anti-silencing function 1 protein |
ATM | Ataxia Telangectasia Mutated |
ATR | Ataxia Telangectasia and Rad3-related protein |
BAF | BRG1-associated factor |
BAMBI | BMP and Activin Membrane-Bound Inhibitor |
BAP1 | BRCA1-associated protein 1 |
BER | Base Excision Repair |
CAF-1 | Chromatin assembly factor-1 |
cBAF | Canonical BAF |
CBP | cAMP-response element binding protein |
CD | Co-directional |
CFSs | Common Fragile Sites |
CPEO | Chronic Progressive External Ophthalmoplegia |
CSB | Cockayne syndrome group B |
CSR | Class-Switch Recombination |
DIP-seq | DNA immunoprecipitation sequencing |
DRIP-Seq | DNA–RNA Immuno-Precipitation sequencing |
DRIPc-Seq | DNA-RNA Immuno-Precipitation followed by cDNA conversion coupled to high-throughput sequencing |
DSB | Double-strand break |
ERFSs | Early Replicating Fragile Sites |
ESCs | Mouse embryonic stem cells |
FA | Fanconi Anemia |
FACT | Facilitates chromatin transcription |
G4 | G-quadruplex |
GLP | G9a-like protein |
HAT | Histone acetyltransferase |
HBD | Hybrid binding domain |
HO | Head-on |
HP1 | Heterochromatin protein 1 |
HR | Homologous Recombination |
ICLs | Inter-strand crosslinks |
Ig | Immunoglobulin |
iPSCs | induced pluripotent stem cells |
m6A | N6-methyladenosine |
MEFs | Mouse Embryonic Fibroblasts |
METTL3 | Methyltransferase-like protein 3 |
miRNA | microRNA |
MMEJ | Micro-homology-Mediated End Joining |
MMR | Mismatch Repair |
MRN | Mre11-Rad50-Nbs1 |
mRNP | messenger ribonucleoprotein |
ncBAF | Non-canonical BAF |
NHEJ | Non-Homologous End-Joining |
PAF-1 | RNAPII-Associated Factor 1 |
PCNA | Proliferating cell nuclear antigen |
PRC | Polycomb Repressor Complex |
PTMs | Post-translational modifications |
RBPs | RNA-Binding Proteins |
rDNA | ribosomal DNA |
REZ | R-loop Elongation Zones |
RFSs | Rare Fragile Sites |
RIZ | R-loop Initiation Zones |
RLFS | R-loop Forming Sequence |
RNAPII | RNA polymerase II |
RNF168 | Ring Finger protein 168 |
rNMPs | ribonucleotide monophosphates |
R-T | Replication-Transcription |
SETX | Senataxin |
SWI/SNF | SWItch/Sucrose Non-Fermentable |
TA-HRR | Transcription-Associated Homologous Recombination Repair |
TAM | Transcription-associated mutagenesis |
TAR | Transcription-associated recombination |
TC-NER | Transcription-Coupled Nucleotide Excision Repair |
TDRD3 | Tudor domain-containing protein 3 complex |
TERRA | Telomeric-Repeat-containing RNA |
TGFβ | Transforming growth factor beta |
TonEBP | Tonicity-responsive enhancer binding protein |
TOP1 | DNA topoisomerase 1 |
TOP2A | DNA topoisomerase 2-alpha |
TOP2B | DNA topoisomerase 2-beta |
TOP3B | DNA topoisomerase 3 Beta |
UFBs | Ultra-fine anaphase bridges |
XPG | Xeroderma Pigmentosum group G |
Xrn2 | 5′-3′ exoribonuclease 2 |
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Chro-Mates | Homologues | Activity | Role in R-Loop Processing | Ref. |
EHMT2/G9a | DmeI (Drosophila melanogaster) | Modifier | Methylation of H3K9me2 at heterochromatin regions | [150,153,158] |
SIRT6 | Sirt6 (Mus musculus) Hst3/4 (Saccharomyces cerevisiae) | Modifier | Deacetylation of H3K56ac | [159,160] |
SIRT7 | Sirt7 (Mus musculus) | Modifier | Deacetylation of DDX21 Histone desuccinylation | [110,161,162] |
Sin3A | Sin3 (Saccharomyces cerevisiae) | Modifier | Histone deacetylation through interaction with THO complex | [163] |
RNF168 | Rnf168 (Mus musculus) | Modifier | Ubiquitination of DHX9 | [164] |
MDM2 | Mdm2 (Mus musculus) | Remodeler | Ubiquitination of H2AK119 and genome expression | [165] |
ATRX | Atrx (Mus musculus) | Remodeler | Antagonization of TERRA RNA at telomeric R-loops | [166,167] |
FACT/SETD2 | yFACT/Set2 (Saccharomyces cerevisiae) | Remodeler | Nucleosome reassembly after RNAPII passage | [168,169] |
INO80 | Ino80 (Saccharomyces cerevisiae) | Remodeler | Chromatin relaxation | [170,171] |
BRG1 | Swi (Saccharomyces cerevisiae) | Remodeler | Regulation of chromatin accessibility | [172] |
Fft3/SMARCAD1 | Fun30 (Saccharomyces cerevisiae) Fft3 (Schizosaccharomyces pombe) | Remodeler | Nucleosome turn-over Active fork protection | [173,174,175,176] |
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Uruci, S.; Lo, C.S.Y.; Wheeler, D.; Taneja, N. R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde. Int. J. Mol. Sci. 2021, 22, 8850. https://doi.org/10.3390/ijms22168850
Uruci S, Lo CSY, Wheeler D, Taneja N. R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde. International Journal of Molecular Sciences. 2021; 22(16):8850. https://doi.org/10.3390/ijms22168850
Chicago/Turabian StyleUruci, Sidrit, Calvin Shun Yu Lo, David Wheeler, and Nitika Taneja. 2021. "R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde" International Journal of Molecular Sciences 22, no. 16: 8850. https://doi.org/10.3390/ijms22168850