Esc2 promotes Mus81 complex-activity via its SUMO-like and DNA binding domains.
Replication across damaged DNA templates is accompanied by transient formation of sister chromatid junctions (SCJs). Cells lacking Esc2, an adaptor protein containing no known enzymatic domains, are defective in the metabolism of these SCJs. However, how Esc2 is involved in the metabolism of SCJs remains elusive. Here we show interaction between Esc2 and a structure-specific endonuclease Mus81-Mms4 (the Mus81 complex), their involvement in the metabolism of SCJs, and the effects Esc2 has on the enzymatic activity of the Mus81 complex. We found that Esc2 specifically interacts with the Mus81 complex via its SUMO-like domains, stimulates enzymatic activity of the Mus81 complex in vitro, and is involved in the Mus81 complex-dependent resolution of SCJs in vivo Collectively, our data point to the possibility that the involvement of Esc2 in the metabolism of SCJs is, in part, via modulation of the activity of the Mus81 complex.
National Centre for Biomolecular Research, Masaryk University, Kamenice 5/A4, CZ-62500 Brno, Czech Republic.|Department of Biology, Masaryk University, Kamenice 5/A7, CZ-62500 Brno, Czech Republic.|IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, IT-20139 Milan, Italy.
Marek
M
Sebesta
IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, IT-20139 Milan, Italy.
Madhusoodanan
M
Urulangodi
National Centre for Biomolecular Research, Masaryk University, Kamenice 5/A4, CZ-62500 Brno, Czech Republic.|Department of Biology, Masaryk University, Kamenice 5/A7, CZ-62500 Brno, Czech Republic.|International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, Pekarska 53, CZ-656 91 Brno, Czech Republic.
Barbora
B
Stefanovie
IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, IT-20139 Milan, Italy.
Barnabas
B
Szakal
National Centre for Biomolecular Research, Masaryk University, Kamenice 5/A4, CZ-62500 Brno, Czech Republic.
Martin
M
Pacesa
Department of Biology, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Michael
M
Lisby
IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, IT-20139 Milan, Italy.
Dana
D
Branzei
National Centre for Biomolecular Research, Masaryk University, Kamenice 5/A4, CZ-62500 Brno, Czech Republic lkrejci@chemi.muni.cz.|Department of Biology, Masaryk University, Kamenice 5/A7, CZ-62500 Brno, Czech Republic.|International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, Pekarska 53, CZ-656 91 Brno, Czech Republic.
Lumir
L
Krejci
D018797:Cell Cycle Proteins; D002842:Chromatids / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D004249:DNA Damage; D004261:DNA Replication; D045566:DNA, Cruciform / Q000737:chemistry / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D042822:Genomic Instability; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D045566:DNA, Cruciform; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C532918:Esc2 protein, S cerevisiae; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D004720:Endonucleases; C411624:MUS81 protein, S cerevisiae
Mol Cell. 2000 Oct;6(4):769-80
11090616
FEBS Lett. 2011 Sep 16;585(18):2861-7
21605556
J Biol Chem. 2002 Apr 26;277(17):14379-89
11825897
J Biol Chem. 2003 Feb 28;278(9):6928-35
12473680
J Cell Biol. 2011 Nov 28;195(5):739-49
22123861
Cell. 2001 Nov 16;107(4):537-48
11719193
PLoS Genet. 2010 Nov 11;6(11):e1001205
21085632
Nature. 2015 Dec 10;528(7581):286-90
26633632
Proteins. 2004 May 1;55(2):330-8
15048824
Nat Genet. 2000 Jun;25(2):192-4
10835635
Genes Dev. 2014 Jul 15;28(14):1604-19
25030699
Nature. 1993 Apr 29;362(6423):860-2
8479526
DNA Repair (Amst). 2007 Jul 1;6(7):1004-17
17409028
Nature. 2008 Dec 18;456(7224):915-20
19092928
Nature. 2008 Nov 20;456(7220):357-61
19020614
Nat Commun. 2012 Mar 20;3:751
22434194
BMC Bioinformatics. 2005 Feb 07;6:22
15698469
Cell. 2012 Nov 9;151(4):807-20
23122649
FEBS Lett. 2014 Aug 1;588(15):2446-56
24928444
J Biol Chem. 2003 Jun 13;278(24):21715-20
12686547
Cold Spring Harb Symp Quant Biol. 2015 ;80:103-9
26370409
Nucleic Acids Res. 2015 Apr 20;43(7):3626-42
25765656
Mol Cell. 2010 Jun 11;38(5):649-61
20541998
Nat Cell Biol. 2013 May;15(5):526-32
23624404
Nat Struct Mol Biol. 2010 Nov;17(11):1377-82
20935631
Cell. 1989 Feb 24;56(4):619-30
2645056
Science. 2015 Aug 14;349(6249):742-7
26273056
Mol Biol Cell. 2009 Mar;20(6):1683-94
19158388
J Biol Chem. 2009 Apr 17;284(16):10387-99
19208620
DNA Repair (Amst). 2005 Feb 3;4(2):243-51
15590332
EMBO J. 2000 Jul 17;19(14):3811-21
10899134
J Biol Chem. 2007 Sep 28;282(39):28971-9
17693398
Nucleic Acids Res. 2012 Jul;40(13):5795-818
22467216
Nat Cell Biol. 2013 Aug;15(8):1008-15
23811686
Genes Dev. 2015 Oct 1;29(19):2067-80
26443850
Nat Struct Mol Biol. 2014 Oct;21(10):884-92
25195051
J Biol Chem. 2014 Feb 28;289(9):5674-86
24443562
Mol Cell Biol. 2011 May;31(9):1921-33
21343337
Cell. 2011 Sep 30;147(1):158-72
21962513
Nat Rev Mol Cell Biol. 2010 Mar;11(3):208-19
20177396
Annu Rev Genet. 2013;47:167-86
24016193
Nucleic Acids Res. 2008 Apr;36(7):2182-95
18281703
DNA Repair (Amst). 2010 Apr 4;9(4):394-402
20106725
J Biol Chem. 2000 Apr 7;275(14):10498-505
10744741
Biopolymers. 1995;37(4):281-92
7540055
Nat Cell Biol. 2015 Nov;17(11):1401-11
26502056
FEBS Lett. 2011 Sep 16;585(18):2810-7
21539841
Science. 1996 Sep 6;273(5280):1392-5
8703075
EMBO J. 2013 Apr 17;32(8):1155-67
23531881
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18249-54
19017809
Cell. 2012 Apr 13;149(2):334-47
22500800
J Biol Chem. 2003 Jul 4;278(27):25172-8
12721304
Cell. 2007 Jul 27;130(2):259-72
17662941
J Biol Chem. 2003 Jan 17;278(3):1618-25
12424238
Genes Dev. 2003 Jul 15;17(14):1768-78
12832395
Nat Cell Biol. 2013 Aug;15(8):1001-7
23811685
Mol Cell. 2001 Nov;8(5):1117-27
11741546
J Biol Chem. 2016 Apr 1;291(14):7594-607
26861880
Mol Biol Cell. 2009 Mar;20(6):1671-82
19158389
J Biol Chem. 2005 Dec 2;280(48):40122-9
16204249
Mol Cell. 2010 Dec 22;40(6):988-1000
21172663
Mol Gen Genet. 2000 Jun;263(5):812-27
10905349
Mol Cell. 2008 Aug 8;31(3):313-23
18691964
Nucleic Acids Res. 2012 Sep 1;40(17):8325-35
22730299
Mol Cell. 2012 Sep 28;47(6):886-96
22885009
J Biol Chem. 2009 Mar 20;284(12):7733-45
19129197
Nature. 2009 Oct 22;461(7267):1071-8
19847258
Mol Cell. 2013 Feb 7;49(3):536-46
23260657
Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15954-9
16247017
Methods Mol Biol. 2012;920:433-43
22941621
Nature. 2003 Dec 18;426(6968):870-4
14685245
EMBO J. 2003 Aug 15;22(16):4304-13
12912927