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 signaling pathway for antiviral innate immune responses [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 research, loss of Ddx11 causes replication stress and sensitizes cancer cells to DNA-damaging agents, such as PARP inhibitors and platinum drugs. It acts downstream of 53BP1 to mediate homology-directed repair and RAD51 focus formation, non-redundantly with BRCA1 and BRCA2. Ddx11 down-regulation aggravates the chemotherapeutic sensitivity of BRCA1/2-mutated cancers [4]. In hepatocellular carcinoma, a high level of Ddx11 is associated with advanced clinical characteristics and poor prognosis, and targeting Ddx11 can promote PARP inhibitor sensitivity by attenuating BRCA2-RAD51 mediated homologous recombination [3].

In conclusion, Ddx11 is essential for genome stability maintenance, DNA replication, and sister chromatid cohesion. Its dysfunction is linked to Warsaw breakage syndrome. In the context of cancer, Ddx11 shows potential as a therapeutic target, as its loss can enhance the sensitivity of cancer cells to certain drugs. Research on Ddx11, especially through loss-of-function models, helps in understanding its role in disease-related biological processes and may offer new strategies for treating associated diseases.