title: Centrosomal Chk2 in DNA damage responses and cell cycle progression.
abstract: Two major control systems regulate early stages of mitosis: activation of Cdk1 and anaphase control through assembly and disassembly of the mitotic spindle. In parallel to cell cycle progression, centrosomal duplication is regulated through proteins including Nek2. Recent studies suggest that centrosome-localized Chk1 forestalls premature activation of centrosomal Cdc25b and Cdk1 for mitotic entry, whereas Chk2 binds centrosomes and arrests mitosis only after activation by ATM and ATR in response to DNA damage. Here, we show that Chk2 centrosomal binding does not require DNA damage, but varies according to cell cycle progression. These and other data suggest a model in which binding of Chk2 to the centrosome at multiple cell cycle junctures controls co-localization of Chk2 with other cell cycle and centrosomal regulators.
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Amnon
authors.initials: A
authors.lastname: Golan
authors.forename: Elah
authors.initials: E
authors.lastname: Pick
authors.forename: Lyuben
authors.initials: L
authors.lastname: Tsvetkov
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Nadler
authors.forename: Harriet
authors.initials: H
authors.lastname: Kluger
authors.forename: David F
authors.initials: DF
authors.lastname: Stern
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000528:radiation effects; D018385:Centrosome / Q000201:enzymology* / Q000528:radiation effects; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D005720:Gamma Rays; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D011485:Protein Binding / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification
chemical_list: D007527:Isoenzymes; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase