The N-terminal region of RECQL4 lacking the helicase domain is both essential and sufficient for the viability of vertebrate cells: Role of the N-terminal region of RECQL4 in cells

Rothmund–Thomson syndrome (RTS) is a rare genetic disorder characterized by premature aging, developmental abnormalities, and a predisposition to cancer. RTS is caused by mutations in the RECQL4 gene, which encodes one of the five human RecQ helicases. To identify the cellular functions of RECQL4, we generated a chicken DT40 cell line in which RECQL4 expression could be turned off by doxycycline (Dox). Upon exposure to Dox, cells stopped growing and underwent apoptosis. The cells could be rescued by expression of the N-terminal region of RECQL4 (amino acids 1–496), which lacks the helicase domain and has sequence similarity to yeast Sld2, which plays an essential function in the initiation of DNA replication in Saccharomyces cerevisiae. Smaller fragments of the N-terminal region of RECQL4 did not rescue the cells from lethality. RECQL4 gene knockout cells complemented with RECQL4 (1–496) showed relatively high sensitivity to DNA damaging agents that induce double strand breaks and cross-links, suggesting that the C-terminal region including the helicase domain of RECQL4 is involved in the repair of certain types of DNA lesions.

Research Highlights
► The N-terminal region of RECQL4 is sufficient for the viability of vertebrate cells. (84)
► The helicase domain of RECQL4 is not necessary for viability. (61)
► The C-terminal region of RECQL4 is involved in the repair of DNA lesions. (73)