Role and Regulation of the RECQL4 Family during Genomic Integrity Maintenance
Abstract
:1. RECQL4 Is Critical in Maintaining DNA Integrity and Disease Prevention
1.1. RECQL4 Is Unique Amongst the RecQ Helicases
1.2. Rothmund-Thomson Syndrome
1.3. Baller-Gerold Syndrome
1.4. RAPADILINO
1.5. RECQL4 in Cancer
2. Model Systems to Study RECQL4 Function
2.1. Due to Difficulties Studying RECQL4 Function in Mice, Other Model Systems Have Been Used
2.2. Yeast Has Been Critical in Studying the Functions of RecQ Helicases
3. Conserved Role for the RECQL4 Family during DNA Replication
3.1. Xenopus RECQL4 Role in Replication Initiation
3.2. Drosophila RECQL4 Role in Replication Initiation
3.3. Human RECQL4 Role in Replication Initiation
4. Role of Hrq1 and RECQL4 during Telomeric DNA Maintenance
4.1. Human RECQL4 Role in Telomeric DNA Maintenance
4.2. Yeast Hrq1 Role during Telomeric DNA Maintenance
5. Role of RECQL4 during DNA Double-Strand Break Repair
5.1. Human and Xenopus RECQL4 Role during Double-Strand Break Repair
5.2. RECQL4 Role during Non-Homologous End Joining
5.3. RECQL4 Role during Homologous Recombination
5.4. Ubiquitylation of RECQL4 during DSB Repair
6. Role of RECQL4 during Base Excision Repair
6.1. RTS Cells Are Sensitive to Oxidizing Agents
6.2. RECQL4 Localizes to Sites of Oxidized DNA Damage
6.3. RECQL4 Interacts with Key BER Proteins
7. Role of RECQL4 during Nucleotide Excision Repair
8. Role of Hrq1 and RECQL4 during DNA Crosslink Repair
9. Role of RECQL4 in Mitochondrial Maintenance
9.1. RECQL4 Localizes to the Mitochondria
9.2. RECQL4 Mitochondrial Localization Is Critical for Sequestering p53 and Enhancing Mitochondrial DNA Replication
9.3. Cells Deficient in RECQL4 Mitochondrial Localization Has Perturbed Bioenergetics
10. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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AP | Apurinic |
ATM | Ataxia-telangiectasia mutated |
BER | Base excision repair |
BGS | Baller-Gerold syndrome |
BLM | Bloom syndrome protein |
CPD | Cyclobutane pyrimidine dimers |
CMG | CDC45-MCM2-7-GINS |
DSB | Double-strand break |
DSBR | Double-strand break repair |
IP | Immunoprecipitation |
IR | Ionizing radiation |
MLS | Mitochondrial localization sequence |
mtDNA | Mitochondria DNA |
NER | Nucleotide excision repair |
NHEJ | Non-Homologous End Joining |
NLS | Nuclear localization sequence |
RTS | Rothmund-Thomson syndrome |
xRTS | Xenopus RECQL4 |
TIFs | Telomere dysfunction-induced foci |
UV | Ultraviolet |
WRN | Werner syndrome ATP-dependent helicase |
Process | Protein | Detection Methods * | Interaction Region | Function | References |
---|---|---|---|---|---|
Localization | p300 | Co-IP, Co-Loc, Pull Down | 1–408 aa | RECQL4 cellular localization | [9] |
Replication | Cut5 | Co-IP | N-terminus | DNA Replication, Xenopus Cut5 with xRTS | [48] |
MCM7 | Co-IP, MS | ND | DNA Replication | [49] | |
MCM10 | Co-IP, MS, Pull Down | 1–200 aa | DNA Replication, inhibition of RECQL4 helicase activity | [49] | |
SLD5 | Co-IP, MS | ND | DNA Replication | [49] | |
Telomere | TRF1 | Co-Loc | ND | Telomere maintenance, Stimulates RECQL4 helicase activity | [50] |
TRF2 | Co-IP | ND | Telomere maintenance, Stimulates RECQL4 helicase activity | [50] | |
WRN | Co-IP | ND | RECQL4 stimulates WRN telomeric D-loop resolution | [50] | |
DSB Repair | BLM | Co-IP, Y2H | 1–471 aa | Increase RECQL4 retention time at DSB sites, BLM stimulation | [51] |
KU70 | Co-IP | N-terminus | NHEJ, RECQL4 enhances KU complex DNA binding. KU inhibits RECQL4 helicase activity | [52] | |
KU80 | Co-IP | ND | NHEJ, RECQL4 enhances KU complex DNA binding. KU inhibits RECQL4 helicase activity | [52] | |
MRE11 | Co-Loc, IP, Pull Down | N-terminus | HR, DNA end resection | [53] | |
RAD51 | Co-Loc, Co-IP | ND | DSB Repair | [54] | |
BER | APE1 | Co-Loc | ND | APE1 endonuclease stimulation | [55] |
FEN1 | Co-Loc | ND | FEN1 incision stimulation | [55] | |
OGG1 | Co-IP | N-terminus | Stimulates OGG1 AP lyase activity | [56] | |
PARP1 | Co-IP, PDS | 833–1208 aa | Base excision repair | [57] | |
POL β | ND | ND | Stimulates POLβ DNA synthesis activity | [55] | |
NER | XPA | Co-IP, Co-Loc, Fractionation, Pull Down | ND | Nucleotide excision repair | [58] |
Mitochondria | p53 | Co-IP, Co-Loc, Fractination | 270–400 aa | Sequestering p53 from nucleus, mtDNA synthesis | [44] |
TOM20 | Pull Down | 13–18 aa | Mitochondrial import | [44] |
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Luong, T.T.; Bernstein, K.A. Role and Regulation of the RECQL4 Family during Genomic Integrity Maintenance. Genes 2021, 12, 1919. https://doi.org/10.3390/genes12121919
Luong TT, Bernstein KA. Role and Regulation of the RECQL4 Family during Genomic Integrity Maintenance. Genes. 2021; 12(12):1919. https://doi.org/10.3390/genes12121919
Chicago/Turabian StyleLuong, Thong T., and Kara A. Bernstein. 2021. "Role and Regulation of the RECQL4 Family during Genomic Integrity Maintenance" Genes 12, no. 12: 1919. https://doi.org/10.3390/genes12121919