Ddx11-flox Mouse

Ddx11, also known as ChlR1, is a super-family two iron-sulfur cluster containing DNA helicase. It plays crucial roles in DNA replication, sister chromatid cohesion establishment, and maintaining general chromosome architecture. It is also involved in the RIG-I-MAVS-mediated antiviral innate immune response [1,5].

Bi-allelic mutations of the Ddx11 gene cause Warsaw breakage syndrome, characterized by growth defects, microcephaly, intellectual disability, heart anomalies, and sister chromatid cohesion loss at the cellular level [1,2]. In cancer, loss of Ddx11 causes replication stress, sensitizes cancer cells to DNA-damaging agents like PARP inhibitors and platinum drugs, and may have an oncogenic role [1,4]. In hepatocellular carcinoma, high levels of wild-type Ddx11 confer resistance to PARP inhibitors due to enhanced recombination repair, while a key mutation (Q238H) can increase susceptibility [3].

In conclusion, Ddx11 is essential for genome stability maintenance, DNA replication, and sister chromatid cohesion. Its dysfunction is associated with Warsaw breakage syndrome and plays a role in cancer development and response to treatment. The study of Ddx11 through loss-of-function models helps to understand its functions in these disease conditions, providing potential therapeutic targets for cancer treatment [2-4,6].