title: The Enok acetyltransferase complex interacts with Elg1 and negatively regulates PCNA unloading to promote the G1/S transition.
abstract: KAT6 histone acetyltransferases (HATs) are highly conserved in eukaryotes and are involved in cell cycle regulation. However, information regarding their roles in regulating cell cycle progression is limited. Here, we report the identification of subunits of the Drosophila Enok complex and demonstrate that all subunits are important for its HAT activity. We further report a novel interaction between the Enok complex and the Elg1 proliferating cell nuclear antigen (PCNA)-unloader complex. Depletion of Enok in S2 cells resulted in a G1/S cell cycle block, and this block can be partially relieved by depleting Elg1. Furthermore, depletion of Enok reduced the chromatin-bound levels of PCNA in both S2 cells and early embryos, suggesting that the Enok complex may interact with the Elg1 complex and down-regulate its PCNA-unloading function to promote the G1/S transition. Supporting this hypothesis, depletion of Enok also partially rescued the endoreplication defects in Elg1-depleted nurse cells. Taken together, our study provides novel insights into the roles of KAT6 HATs in cell cycle regulation through modulating PCNA levels on chromatin.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA; Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan;
authors.forename: Fu
authors.initials: F
authors.lastname: Huang
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Anita
authors.initials: A
authors.lastname: Saraf
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA;
authors.forename: Thomas
authors.initials: T
authors.lastname: Kusch
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Leanne T
authors.initials: LT
authors.lastname: Szerszen
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Arnob
authors.initials: A
authors.lastname: Dutta
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA; Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA;
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA; Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Abmayr
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; C000614371:Elg1 protein, Drosophila; D018809:Proliferating Cell Nuclear Antigen; D021122:Protein Subunits; C000595040:Enok protein, Drosophila; D051548:Histone Acetyltransferases
keywords: PCNA unloading; cell cycle progression; chromatin; histone acetyltransferase