Impairing Cohesin Smc1/3 Head Engagement Compensates for the Lack of Eco1 Function.
The cohesin ring, which is composed of the Smc1, Smc3, and Scc1 subunits, topologically embraces two sister chromatids from S phase until anaphase to ensure their precise segregation to the daughter cells. The opening of the ring is required for its loading on the chromosomes and unloading by the action of Wpl1 protein. Both loading and unloading are dependent on ATP hydrolysis by the Smc1 and Smc3 "head" domains, which engage to form two composite ATPase sites. Based on the available structures, we modeled the Saccharomyces cerevisiae Smc1/Smc3 head heterodimer and discovered that the Smc1/Smc3 interfaces at the two ATPase sites differ in the extent of protein contacts and stability after ATP hydrolysis. We identified smc1 and smc3 mutations that disrupt one of the interfaces and block the Wpl1-mediated release of cohesin from DNA. Thus, we provide structural insights into how the cohesin heads engage with each other.
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 138671 Singapore, Singapore.
Roland G
RG
Huber
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 138671 Singapore, Singapore.
Irina
I
Kulemzina
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 138671 Singapore, Singapore.
Keven
K
Ang
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 138671 Singapore, Singapore.
Alap P
AP
Chavda
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 138671 Singapore, Singapore.
Sasikala
S
Suranthran
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 138671 Singapore, Singapore.
Jun-Thing
JT
Teh
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 138671 Singapore, Singapore.
Dimitar
D
Kenanov
Institute of Medical Biology (IMB), Agency for Science, Technology and Research (A(∗)STAR), 138648 Singapore, Singapore; School of Biological Sciences, Nanyang Technological University (NTU), 637551 Singapore, Singapore.
Gaowen
G
Liu
Institute of Medical Biology (IMB), Agency for Science, Technology and Research (A(∗)STAR), 138648 Singapore, Singapore.
Giulia
G
Rancati
Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A(∗)STAR), 138673 Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (NUS), 117597 Singapore, Singapore.
Radoslaw
R
Szmyd
Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A(∗)STAR), 138673 Singapore, Singapore; Department of Biochemistry, National University of Singapore (NUS), 117597 Singapore, Singapore.
Philipp
P
Kaldis
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 138671 Singapore, Singapore; Department of Biological Sciences (DBS), National University of Singapore (NUS), 117543 Singapore, Singapore. Electronic address: peterjb@bii.a-star.edu.sg.
Peter J
PJ
Bond
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 138671 Singapore, Singapore; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A(∗)STAR), 138673 Singapore, Singapore; Department of Physics, National University of Singapore (NUS), 117551 Singapore, Singapore. Electronic address: dmitryi@bii.a-star.edu.sg.
Dmitri
D
Ivanov
D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry*; D020816:Amino Acid Motifs; D001665:Binding Sites; D020134:Catalytic Domain; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002842:Chromatids / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D006868:Hydrolysis; D008958:Models, Molecular; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
D000123:Acetyltransferases; D000255:Adenosine Triphosphate; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1; C476199:RAD61 protein, S cerevisiae; C120372:SMC3 protein, S cerevisiae; C118076:ECO1 protein, S cerevisiae
cohesin; molecular dynamics simulation; protein-protein interactions; sister chromatid cohesion