A conserved domain in the scc3 subunit of cohesin mediates the interaction with both mcd1 and the cohesin loader complex.
The Structural Maintenance of Chromosome (SMC) complex, termed cohesin, is essential for sister chromatid cohesion. Cohesin is also important for chromosome condensation, DNA repair, and gene expression. Cohesin is comprised of Scc3, Mcd1, Smc1, and Smc3. Scc3 also binds Pds5 and Wpl1, cohesin-assoc...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-03-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4352044?pdf=render |
| _version_ | 1818439194821787648 |
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| author | Ola Orgil Avi Matityahu Thomas Eng Vincent Guacci Douglas Koshland Itay Onn |
| author_facet | Ola Orgil Avi Matityahu Thomas Eng Vincent Guacci Douglas Koshland Itay Onn |
| author_sort | Ola Orgil |
| collection | DOAJ |
| description | The Structural Maintenance of Chromosome (SMC) complex, termed cohesin, is essential for sister chromatid cohesion. Cohesin is also important for chromosome condensation, DNA repair, and gene expression. Cohesin is comprised of Scc3, Mcd1, Smc1, and Smc3. Scc3 also binds Pds5 and Wpl1, cohesin-associated proteins that regulate cohesin function, and to the Scc2/4 cohesin loader. We mutagenized SCC3 to elucidate its role in cohesin function. A 5 amino acid insertion after Scc3 residue I358, or a missense mutation of residue D373 in the adjacent stromalin conservative domain (SCD) induce inviability and defects in both cohesion and cohesin binding to chromosomes. The I358 and D373 mutants abrogate Scc3 binding to Mcd1. These results define an Scc3 region extending from I358 through the SCD required for binding Mcd1, cohesin localization to chromosomes and cohesion. Scc3 binding to the cohesin loader, Pds5 and Wpl1 are unaffected in I358 mutant and the loader still binds the cohesin core trimer (Mcd1, Smc1 and Smc3). Thus, Scc3 plays a critical role in cohesin binding to chromosomes and cohesion at a step distinct from loader binding to the cohesin trimer. We show that residues Y371 and K372 within the SCD are critical for viability and chromosome condensation but dispensable for cohesion. However, scc3 Y371A and scc3 K372A bind normally to Mcd1. These alleles also provide evidence that Scc3 has distinct mechanisms of cohesin loading to different loci. The cohesion-competence, condensation-incompetence of Y371 and K372 mutants suggests that cohesin has at least one activity required specifically for condensation. |
| first_indexed | 2024-12-14T17:52:36Z |
| format | Article |
| id | doaj.art-a63c9771bf9b43a48bfaae1dea76198b |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-14T17:52:36Z |
| publishDate | 2015-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-a63c9771bf9b43a48bfaae1dea76198b2022-12-21T22:52:37ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-03-01113e100503610.1371/journal.pgen.1005036A conserved domain in the scc3 subunit of cohesin mediates the interaction with both mcd1 and the cohesin loader complex.Ola OrgilAvi MatityahuThomas EngVincent GuacciDouglas KoshlandItay OnnThe Structural Maintenance of Chromosome (SMC) complex, termed cohesin, is essential for sister chromatid cohesion. Cohesin is also important for chromosome condensation, DNA repair, and gene expression. Cohesin is comprised of Scc3, Mcd1, Smc1, and Smc3. Scc3 also binds Pds5 and Wpl1, cohesin-associated proteins that regulate cohesin function, and to the Scc2/4 cohesin loader. We mutagenized SCC3 to elucidate its role in cohesin function. A 5 amino acid insertion after Scc3 residue I358, or a missense mutation of residue D373 in the adjacent stromalin conservative domain (SCD) induce inviability and defects in both cohesion and cohesin binding to chromosomes. The I358 and D373 mutants abrogate Scc3 binding to Mcd1. These results define an Scc3 region extending from I358 through the SCD required for binding Mcd1, cohesin localization to chromosomes and cohesion. Scc3 binding to the cohesin loader, Pds5 and Wpl1 are unaffected in I358 mutant and the loader still binds the cohesin core trimer (Mcd1, Smc1 and Smc3). Thus, Scc3 plays a critical role in cohesin binding to chromosomes and cohesion at a step distinct from loader binding to the cohesin trimer. We show that residues Y371 and K372 within the SCD are critical for viability and chromosome condensation but dispensable for cohesion. However, scc3 Y371A and scc3 K372A bind normally to Mcd1. These alleles also provide evidence that Scc3 has distinct mechanisms of cohesin loading to different loci. The cohesion-competence, condensation-incompetence of Y371 and K372 mutants suggests that cohesin has at least one activity required specifically for condensation.http://europepmc.org/articles/PMC4352044?pdf=render |
| spellingShingle | Ola Orgil Avi Matityahu Thomas Eng Vincent Guacci Douglas Koshland Itay Onn A conserved domain in the scc3 subunit of cohesin mediates the interaction with both mcd1 and the cohesin loader complex. PLoS Genetics |
| title | A conserved domain in the scc3 subunit of cohesin mediates the interaction with both mcd1 and the cohesin loader complex. |
| title_full | A conserved domain in the scc3 subunit of cohesin mediates the interaction with both mcd1 and the cohesin loader complex. |
| title_fullStr | A conserved domain in the scc3 subunit of cohesin mediates the interaction with both mcd1 and the cohesin loader complex. |
| title_full_unstemmed | A conserved domain in the scc3 subunit of cohesin mediates the interaction with both mcd1 and the cohesin loader complex. |
| title_short | A conserved domain in the scc3 subunit of cohesin mediates the interaction with both mcd1 and the cohesin loader complex. |
| title_sort | conserved domain in the scc3 subunit of cohesin mediates the interaction with both mcd1 and the cohesin loader complex |
| url | http://europepmc.org/articles/PMC4352044?pdf=render |
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