title: CHK2 kinase in the DNA damage response and beyond.
abstract: The serine/threonine kinase CHK2 is a key component of the DNA damage response. In human cells, following genotoxic stress, CHK2 is activated and phosphorylates >20 proteins to induce the appropriate cellular response, which, depending on the extent of damage, the cell type, and other factors, could be cell cycle checkpoint activation, induction of apoptosis or senescence, DNA repair, or tolerance of the damage. Recently, CHK2 has also been found to have cellular functions independent of the presence of nuclear DNA lesions. In particular, CHK2 participates in several molecular processes involved in DNA structure modification and cell cycle progression. In this review, we discuss the activity of CHK2 in response to DNA damage and in the maintenance of the biological functions in unstressed cells. These activities are also considered in relation to a possible role of CHK2 in tumorigenesis and, as a consequence, as a target of cancer therapy.
authors.affiliation: Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zannini
authors.affiliation: Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy giacomo.buscemi@unimi.it domenico.delia@istitutotumori.mi.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Delia
authors.affiliation: Department of Biosciences, University of Milan, via Celoria 26, 20133 Milan, Italy giacomo.buscemi@unimi.it domenico.delia@istitutotumori.mi.it.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Buscemi
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064447:Checkpoint Kinase 2 / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D006801:Humans; D010766:Phosphorylation / Q000235:genetics
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human
keywords: DNA damage; apoptosis; checkpoints; genomic stability