Recql5-KO Mouse

Recql5 is a member of the RecQ family of DNA helicases. These helicases play crucial roles in maintaining genome stability, with Recql5 being associated with processes such as DNA repair, replication, and transcription [1,2,3]. It is unique among RecQ helicases as it is associated with RNA polymerase II, the enzyme for transcribing protein-encoding genes in eukaryotes [3].

Studies using Recql5 knockout mice have revealed its significance. Recql5-deficient mice are more cancer-prone and show increased chromosomal instability [2]. Recql5-deficient mouse embryonic fibroblasts are sensitive to camptothecin and display elevated sister chromatid exchanges, similar to cells lacking other RecQ helicases [1]. In non-small cell lung cancer, knockdown of Recql5 in cell lines inhibited invasion, migration, and epithelial-mesenchymal transition, and also increased apoptosis in cisplatin-resistant cells, indicating its role in cancer metastasis and drug resistance [4]. In myeloproliferative neoplasms, Recql5 expression is increased in JAK2V617F-expressing cells and is required to counteract JAK2V617F-induced replication stress [5].

In conclusion, Recql5 is essential for maintaining genome stability through its involvement in DNA-related processes. Gene knockout mouse models have been instrumental in demonstrating its role in cancer-related processes such as tumorigenesis, metastasis, and drug resistance, as well as in conditions like myeloproliferative neoplasms. These findings provide insights into potential therapeutic targets for treating related diseases.

References:

1. Hamadeh, Zeid, Lansdorp, Peter. 2020. RECQL5 at the Intersection of Replication and Transcription. In Frontiers in cell and developmental biology, 8, 324. doi:10.3389/fcell.2020.00324. https://pubmed.ncbi.nlm.nih.gov/32523948/

2. Popuri, Venkateswarlu, Tadokoro, Takashi, Croteau, Deborah L, Bohr, Vilhelm A. 2013. Human RECQL5: guarding the crossroads of DNA replication and transcription and providing backup capability. In Critical reviews in biochemistry and molecular biology, 48, 289-99. doi:10.3109/10409238.2013.792770. https://pubmed.ncbi.nlm.nih.gov/23627586/

3. Aygün, Ozan, Svejstrup, Jesper Q. 2010. RECQL5 helicase: connections to DNA recombination and RNA polymerase II transcription. In DNA repair, 9, 345-53. doi:10.1016/j.dnarep.2009.12.008. https://pubmed.ncbi.nlm.nih.gov/20080450/

4. Xia, Hong-Wei, Zhang, Zhi-Qiang, Yuan, Jun, Niu, Qing-Ling. 2020. Human RECQL5 promotes metastasis and resistance to cisplatin in non-small cell lung cancer. In Life sciences, 265, 118768. doi:10.1016/j.lfs.2020.118768. https://pubmed.ncbi.nlm.nih.gov/33217443/

5. Chen, Edwin, Ahn, Jong Sook, Sykes, David B, Green, Anthony R, Mullally, Ann. 2015. RECQL5 Suppresses Oncogenic JAK2-Induced Replication Stress and Genomic Instability. In Cell reports, 13, 2345-2352. doi:10.1016/j.celrep.2015.11.037. https://pubmed.ncbi.nlm.nih.gov/26686625/