RecQ Helicases in DNA Repair and Genomic Stability

RecQ helicases constitute a conserved family of DNA‐unwinding enzymes essential for the maintenance of genome integrity. In humans, five paralogues—RECQL1, BLM, WRN, RECQL4 and RECQL5—coordinate DNA replication, repair and recombination by resolving aberrant DNA secondary structures, facilitating replication‐fork restart and suppressing deleterious chromosomal rearrangements. Loss‐of‐function mutations in these helicases underlie disorders such as Bloom syndrome, Werner syndrome and Rothmund–Thomson syndrome, which are characterised by cancer predisposition, premature ageing and developmental defects. Beyond hereditary syndromes, dysregulation of RecQ activity influences tumour immunogenicity, telomere stability and responses to replicative stress. Interplay with cell‐cycle kinases, ubiquitin ligases and PARP/PARG enzymes determines pathway choice between non‐homologous end joining and homologous recombination, while emerging roles in transcription–replication conflict resolution and chromosomal engineering highlight their broad biological and biomedical significance.

Research from Nature Portfolio

Recent studies have elucidated how post‐translational modification governs RecQ function under stress. One investigation revealed that the ubiquitin ligase Trim33 regulates E2F4 degradation, thereby transiently recruiting RECQL1 to stalled forks in transcriptionally active chromatin. This mechanism promotes fork progression under oncogenic or drug‐induced replicative stress and prevents checkpoint bypass and DNA damage. A foundational work demonstrated that CDK1/2‐mediated phosphorylation of RECQL4 at defined serine residues directs its engagement in either non‐homologous end joining during G1 or homologous recombination in S/G2; subsequent ubiquitination by a DDB1–CUL4A ligase enhances its accumulation at double‐strand breaks, stimulates DNA end resection and optimises repair fidelity.

RecQ Helicases in DNA Repair and Genomic Stability publication trend

The graph below shows the total number of articles in recq helicases in dna repair and genomic stability across all publications each year (not limited to Nature Index journals).

Technical terms

RecQ helicase: A conserved enzyme that unwinds structured DNA to support replication, repair and recombination.

Replication fork: The Y‐shaped junction where parental DNA strands separate to allow synthesis of new strands.

Homologous recombination (HR): A high‐fidelity repair pathway using a homologous sequence as a template to mend DNA double‐strand breaks.

Non‐homologous end joining (NHEJ): A DNA repair process that directly ligates broken DNA ends without requiring sequence homology.

PARylation: The attachment of poly(ADP‐ribose) chains by PARP enzymes to modulate protein function during DNA damage response.

Ubiquitination: The covalent addition of ubiquitin to proteins, which can alter their stability, activity or interactions.

PARG: Poly(ADP‐ribose) glycohydrolase, the enzyme responsible for removing PAR chains and reversing PARylation.

Chromosomal engineering: The deliberate induction of defined chromosomal rearrangements, such as inversions or translocations, often employing CRISPR/Cas9.

References

1. Trim33 masks a non-transcriptional function of E2f4 in replication fork progression. Nature Communications (2023).
2. Cell cycle-dependent phosphorylation regulates RECQL4 pathway choice and ubiquitination in DNA double-strand break repair. Nature Communications (2017).
3. Immune infiltration, aggressive pathology, and poor survival outcomes in RECQL helicase deficient breast cancers. Neoplasia (2023).
4. RECQL4 requires PARP1 for recruitment to DNA damage, and PARG dePARylation facilitates its associated role in end joining. Experimental & Molecular Medicine (2025).
5. A Recql5 mutant facilitates complex CRISPR/Cas9-mediated chromosomal engineering in mouse zygotes. Genetics (2024).
6. Rothmund-Thomson syndrome. Orphanet Journal of Rare Diseases (2010).