The hsSsu72 phosphatase is a cohesin-binding protein that regulates the resolution of sister chromatid arm cohesion.
Cohesin is a multiprotein complex that establishes sister chromatid cohesion from S phase until mitosis or meiosis. In vertebrates, sister chromatid cohesion is dissolved in a stepwise manner: most cohesins are removed from the chromosome arms via a process that requires polo-like kinase 1 (Plk1), aurora B and Wapl, whereas a minor amount of cohesin, found preferentially at the centromere, is cleaved by separase following its activation by the anaphase-promoting complex/cyclosome. Here, we report that our budding yeast two-hybrid assay identified hsSsu72 phosphatase as a Rad21-binding protein. Additional experiments revealed that Ssu72 directly interacts with Rad21 and SA2 in vitro and in vivo, and associates with sister chromatids in human cells. Interestingly, depletion or mutational inactivation of Ssu72 phosphatase activity caused the premature resolution of sister chromatid arm cohesion, whereas the overexpression of Ssu72 yielded high resistance to this resolution. Interestingly, it appears that Ssu72 regulates the cohesion of chromosome arms but not centromeres, and acts by counteracting the phosphorylation of SA2. Thus, our study provides important new evidence, suggesting that Ssu72 is a novel cohesin-binding protein capable of regulating cohesion between sister chromatid arms.
Kim
Hyun-Soo
HS
Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea.
Baek
Kwan-Hyuck
KH
Ha
Geun-Hyoung
GH
Lee
Jae-Chul
JC
Kim
Yu-Na
YN
Lee
Janet
J
Park
Hye-Young
HY
Lee
Noo Ri
NR
Lee
Ho
H
Cho
Yunje
Y
Lee
Chang-Woo
CW
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010749:Phosphoprotein Phosphatases; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D000097722:Cohesins
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010749:Phosphoprotein Phosphatases; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D000097722:Cohesins; C429022:RAD21 protein, human; C496300:SSU72 protein, human
Cell. 2000 Oct 27;103(3):399-410
11081627
Science. 2001 Aug 17;293(5533):1320-3
11509732
Dev Cell. 2006 May;10(5):575-85
16580887
Curr Biol. 2004 Jul 13;14(13):1187-93
15242616
Mol Cell Biol. 2000 Nov;20(22):8343-51
11046131
Mol Cell. 2002 Mar;9(3):515-25
11931760
Mol Cell. 2004 May 7;14(3):387-94
15125841
EMBO J. 2004 Aug 4;23(15):3144-53
15241476
Nature. 2006 May 4;441(7089):46-52
16541025
Nature. 2006 May 4;441(7089):53-61
16541024
J Cell Biol. 2000 Aug 7;150(3):405-16
10931856
Cell. 2002 Feb 22;108(4):439-51
11909516
Nucleic Acids Res. 2005 Jan 19;33(2):464-77
15659578
Methods. 2006 Jan;38(1):17-24
16343937
Cell. 1997 Oct 3;91(1):35-45
9335333
Science. 2007 Jul 13;317(5835):245-8
17626885
J Biol Chem. 2003 May 2;278(18):15917-21
12606538
Curr Biol. 2006 Dec 19;16(24):2406-17
17112726
Science. 2008 Jul 25;321(5888):563-6
18653893
Cancer Res. 2009 Jan 1;69(1):27-36
19117984
J Cell Biol. 2000 Nov 13;151(4):749-62
11076961
Cell. 2006 Dec 1;127(5):955-67
17113138
Science. 2002 Jul 26;297(5581):559-65
12142526
PLoS Biol. 2005 Mar;3(3):e86
15737064
Genes Dev. 1998 Jul 1;12(13):1986-97
9649503
Nature. 2008 Feb 14;451(7180):796-801
18235444
Science. 2007 Jul 13;317(5835):242-5
17626884
Genes Dev. 2002 Dec 1;16(23):3004-16
12464631
PLoS Biol. 2005 Mar;3(3):e69
15737063
EMBO J. 2003 Apr 1;22(7):1588-98
12660165
Mol Cell. 2002 Apr;9(4):773-88
11983169
Science. 2008 Jul 25;321(5888):566-9
18653894