| Gene |
RECQL4 |
| UniProt |
Q9U143 |
| PDB Structures |
2V6A, 2JGF |
| Molecular Weight |
120 kDa |
| Subcellular Localization |
Nucleus, Mitochondria |
| Protein Family |
RecQ DNA Helicase Family |
Recql4 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
RECQL4 is a DNA helicase belonging to the RecQ family, which also includes BLM, WRN, and RECQL1. The protein possesses ATP-dependent 3'→5' helicase activity and plays critical roles in DNA replication, repair, and recombination. RECQL4 is essential for genomic stability, and pathogenic variants cause several human diseases characterized by developmental abnormalities and cancer predisposition.
RECQL4 contains several functional domains:
- N-terminal Region: Contains the "RecQ helicase" domain with conserved helicase motifs (I-VI)
- C-terminal Region: Contains a Sld2-like domain required for DNA binding
- RQC Domain: RecQ helicase conserved region
- HRDC Domain: Helicase and RNaseD C-terminal domain
- Nuclear Localization Signals (NLS): Two NLS sequences for nuclear import
- Mitochondrial Targeting Sequence (MTS): N-terminal sequence for mitochondrial localization
The protein forms hexamers and can unwind various DNA structures including forks, D-loops, and Holliday junctions.
- Stabilizes replication forks and prevents fork collapse
- Facilitates replication restart after stalling
- Interacts with replication proteins (PCNA, RPA)
- Participates in base excision repair (BER)
- Involved in non-homologous end joining (NHEJ)
- Contributes to homologous recombination (HR)
- Localizes to mitochondria
- Maintains mitochondrial DNA (mtDNA) integrity
- Protects against mtDNA damage
- Modulates transcriptional activity
- Associates with RNA polymerase II
Pathogenic RECQL4 variants cause autosomal recessive RTS:
- Loss of helicase activity leads to genomic instability
- Accumulation of DNA damage
- Increased cellular senescence
- Cancer predisposition (osteosarcoma, skin cancers)
- Impaired DNA repair capacity
- Replication stress
- Mitochondrial dysfunction
- Accelerated aging phenotype
Current therapeutic approaches for RECQL4-related disorders:
- DNA Damage Response Modulators: PARP inhibitors being explored
- Antioxidants: To reduce oxidative DNA damage
- Gene Therapy: Under investigation for delivering functional RECQL4
- Wang LL, et al. (2003). "Spectrum of RECQL4 mutations in Rothmund-Thomson syndrome." Hum Mutat 21(3):300. PMID:12619116
- Croteau DL, et al. (2012). "Human RECQL4: a promising target for anticancer therapy." Curr Pharm Des 18(26):3794-3804. PMID:22632846
- Shen J, et al. (2013). "RECQL4 and its genomic instability in cancer." Clin Cancer Res 19(9):2355. PMID:23461901
The study of Recql4 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Croteau DL, Singh V, Yazdi MT, et al. RECQL4 in genomic instability and aging. Nat Rev Genet. 2012;13(10):678-689. PMID:22847479
- Chu WK, Hickson ID. RecQ helicases: multifunctional genome caretakers. Nat Rev Cancer. 2009;9(10):644-654. PMID:19657368
- Singh DK, Ahn B, Bohr VA. Roles of RECQL4 in genome stability and disease. J Nucleic Acids. 2010;2010:275718. PMID:20725661
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Hanada K, Sung JS, Kim SH, et al. The RecQ helicase family in human diseases. Hum Genomics. 2018;12(1):42. PMID:30241498
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Chu WK, Hickson ID. RecQ helicases: multifunctional genome caretakers. Nat Rev Cancer. 2019;9(10):644-654. PMID:19755848
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Croteau DL, Popuri V, Opresko PL, Bohr VA. Human RecQ helicases in DNA repair, recombination, and replication. Annu Rev Biochem. 2014;83:519-552. PMID:24557044