title: Hippo pathway and protection of genome stability in response to DNA damage.
abstract: The integrity of DNA is constantly challenged by exposure to the damaging effects of chemical and physical agents. Elucidating the cellular mechanisms that maintain genomic integrity via DNA repair and cell growth control is vital because errors in these processes lead to genomic damage and the development of cancer. By gaining a deep molecular understanding of the signaling pathways regulating genome integrity it is hoped to uncover new therapeutics and treatment designs to combat cancer. Components of the Hippo pathway, a tumor-suppressor cascade, have recently been defined to limit cancer transformation in response to DNA damage. In this review, we briefly introduce the Hippo signaling cascade in mammals and discuss in detail how the Hippo pathway has been established as part of the DNA damage response, activated by apical signaling kinases that recognize breaks in DNA. We also highlight the significance of the Hippo pathway activator RASSF1A tumor suppressor, a direct target of ataxia telangiectasia mutated and ataxia telangiectasia and Rad3 related ATR. Furthermore we discuss how Hippo pathway in response DNA lesions can induce cell death via Yes-associated protein (YAP) (the canonical Hippo pathway effector) or promote maintenance of genome integrity in a YAP-independent manner.
authors.affiliation: CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, UK.
authors.forename: Dafni E
authors.initials: DE
authors.lastname: Pefani
authors.affiliation: CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, UK.
authors.forename: Eric
authors.initials: E
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D042822:Genomic Instability; D000090683:Hippo Signaling Pathway; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017346:Protein Serine-Threonine Kinases
keywords: DNA damage; Hippo pathway; RASSF1A; YAP; genome integrity