{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRECQL4 is a multifunctional enzyme that plays a central role in the initiation of DNA replication. Its evolutionarily conserved Sld2‐like N‑terminal domain, together with intrinsic ATPase and helicase activities, enables RECQL4 to assist in the assembly of replication complexes by facilitating the chromatin recruitment of key factors such as CDC45, the MCM helicase complex, MCM10, and the GINS complex. Biochemical and cell‐based studies demonstrate that RECQL4 interacts with components of the pre‑replicative complex and the active replicative helicase (CMG) to effectively regulate origin firing and replication fork progression during S phase. These replication‐promoting functions are dependent on both its DNA binding and unwinding activities, as well as the integration of cell cycle–regulated kinases that modulate its interaction with other replication proteins."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its replication‐promoting role, RECQL4 participates actively in the maintenance of genomic integrity by engaging in diverse DNA repair pathways. It contributes to the processing of double‐strand breaks by facilitating DNA end resection—a critical step for homologous recombination repair—and interacts with repair proteins such as MRE11 and CtIP. RECQL4 also influences base excision repair by stimulating the activities of key nucleases and polymerases in response to oxidative damage. In addition, RECQL4 localizes to telomeres and mitochondria where, through associations with shelterin components and mitochondrial factors, it helps resolve D‑loop structures and maintains mitochondrial DNA integrity. These properties underscore its dual role in safeguarding both nuclear and mitochondrial genomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, mutations or dysregulated expression of RECQL4 are associated with a spectrum of disorders—including Rothmund‐Thomson, RAPADILINO, and Baller–Gerold syndromes—which are marked by genomic instability, developmental defects, cancer predisposition, and premature aging. In several cancers, aberrant overexpression of RECQL4 correlates with increased survival of tumor cells, chemoresistance, and aggressive tumor behavior; moreover, its interactions with factors such as BLM, p300, survivin, and even p53 further highlight its multifaceted regulatory influence. Structural and model–organism studies have provided additional insights into its domain organization and the consequences of its misregulation in both replication and repair pathways, emphasizing its pivotal role in cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mahesh N Sangrithi, Juan A Bernal, Mark Madine, et al. 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