Minute amounts of helicase-deficient truncated RECQL4 are sufficient for DNA replication.

ABSTRACT: RECQL4, a RecQ family helicase, is essential for DNA replication and genome stability. Mutations in RECQL4 cause severe human disorders yet we do not fully understand its functions, particularly regarding ATP-dependent helicase activity. To understand RECQL4's functions further, we performed a genome-wide forward genetic screen using a murine model harbouring patient-like RECQL4 mutations. We identify KLHDC3, a substrate-binding subunit of the Cullin-RING ligase E3 complex, loss as the most significant rescue allele. KLHDC3 loss restores proliferation and replication in RECQL4-deficient cells by stabilizing trace levels of a truncated RECQL4 fragment containing the N-terminal 480 amino acids, lacking the helicase and C-terminal regions. This RECQL4 fragment forms after Cre-mediated recombi

SUBMITTER: Paula Armina, Villapa Buco 

PROVIDER: S-SCDT-10_1038-S44319-026-00727-2 | biostudies-other |

REPOSITORIES: biostudies-other