title: Opposing Functions of the N-terminal Acetyltransferases Naa50 and NatA in Sister-chromatid Cohesion.
abstract: During the cell cycle, sister-chromatid cohesion tethers sister chromatids together from S phase to the metaphase-anaphase transition and ensures accurate segregation of chromatids into daughter cells. N-terminal acetylation is one of the most prevalent protein covalent modifications in eukaryotes and is mediated by a family of N-terminal acetyltransferases (NAT). Naa50 (also called San) has previously been shown to play a role in sister-chromatid cohesion in metazoans. The mechanism by which Naa50 contributes to cohesion is not understood however. Here, we show that depletion of Naa50 in HeLa cells weakens the interaction between cohesin and its positive regulator sororin and causes cohesion defects in S phase, consistent with a role of Naa50 in cohesion establishment. Strikingly, co-depletion of NatA, a heterodimeric NAT complex that physically interacts with Naa50, rescues the sister-chromatid cohesion defects and the resulting mitotic arrest caused by Naa50 depletion, indicating that NatA and Naa50 play antagonistic roles in cohesion. Purified recombinant NatA and Naa50 do not affect each other's NAT activity in vitro Because NatA and Naa50 exhibit distinct substrate specificity, we propose that they modify different effectors and regulate sister-chromatid cohesion in opposing ways.
authors.affiliation: From the Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 and.
authors.forename: Ziye
authors.initials: Z
authors.lastname: Rong
authors.affiliation: From the Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 and.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Department of Biochemistry and Biophysics, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Magin
authors.affiliation: Department of Biochemistry and Biophysics, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Ronen
authors.initials: R
authors.lastname: Marmorstein
authors.affiliation: From the Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 and hongtao.yu@utsouthwestern.edu.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yu
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000201:enzymology* / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D002877:Chromosomes, Human / Q000201:enzymology* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D063209:N-Terminal Acetyltransferase A / Q000235:genetics / Q000378:metabolism*; D063213:N-Terminal Acetyltransferase E / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000502:physiology*; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D000097722:Cohesins; C520714:NAA50 protein, human
keywords: N-terminal acetylation; acetyltransferase; cell cycle; chromosomes; cohesin; enzyme; mitosis; sister-chromatid cohesion