Novel mutations in the RECQL4 gene affect its helicase functions, interactions with the BLM helicase and chemotherapeutics-induced cell death.

ABSTRACT: RecQ family of DNA helicases play pivotal roles in DNA replication, repair and responses to DNA damage or replication stress. Several human RecQ helicases are defective in diseases associated with chromosomal instability, premature aging and cancer. We recently discovered novel mutations in the RECQL4 gene in glioblastoma (GBM), the most malignant brain tumor in adults. Transcriptomic profiles of GBMs with REQCL4 mutations resembled those in REQCL4 KO glioma cells. We employ structural modelling and biochemical approaches to elucidate impacts of novel mutations on RECQL4 helicase activities. Using recombinant RECQL4_P532S and RECQL4_R766Q proteins we demonstrate that P532S substitution reduces the RECQL4 ability to unwind DNA and disrupts DNA-coupled ATP-hydrolysis acti

SUBMITTER: Kaczmarczyk A 

PROVIDER: S-EPMC12717039 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature