title: A Blm-Recql5 partnership in replication stress response.
abstract: Deficiencies in DNA damage response and repair not only can result in genome instability and cancer predisposition, but also can render the cancer cells intrinsically more vulnerable to certain types of DNA damage insults. Particularly, replication stress is both a hallmark of human cancers and a common instigator for genome instability and cell death. Here, we review our work based on the genetic knockout studies on Blm and Recql5, two members of the mammalian RecQ helicase family. These studies have uncovered a unique partnership between these two helicases in the implementation of proper mitigation strategies under different circumstances to promote DNA replication and cell survival and suppress genome instability and cancer. In particular, current studies have revealed the presence of a novel Recql5/RECQL5-dependent mechanism for suppressing replication fork collapse in response to global replication fork stalling following exposure to camptothecin (CPT), a topoisomerase I inhibitor, and a potent inhibitor of DNA replication. The unique partnership between Blm and Recql5 in coping with the challenge imposed by replication stress is discussed. In addition, given that irinotecan and topotecan, two CPT derivatives, are currently used in clinic for treating human cancer patients with very promising results, the potential implication of the new findings from these studies in anticancer treatments is also discussed.
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical College, Wenzhou 325027, China.
authors.forename: Xincheng
authors.initials: X
authors.lastname: Lu
authors.forename: Hua
authors.initials: H
authors.lastname: Lou
authors.forename: Guangbin
authors.initials: G
authors.lastname: Luo
mesh_terms: D002166:Camptothecin / Q000494:pharmacology; D004249:DNA Damage; D004261:DNA Replication; D042822:Genomic Instability; D006801:Humans; D053484:RecQ Helicases / Q000235:genetics* / Q000378:metabolism; D012854:Sister Chromatid Exchange; D059003:Topoisomerase Inhibitors / Q000494:pharmacology
chemical_list: C506732:RECQL5 protein, human; D059003:Topoisomerase Inhibitors; C097151:Bloom syndrome protein; D053484:RecQ Helicases; D002166:Camptothecin