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A handcuff model for the cohesin complex.

Zhang N, Kuznetsov SG, Sharan SK, Li K, Rao PH, Pati D - J. Cell Biol. (2008)

Bottom Line: Several models for the cohesin complex have been proposed, but the one-ring embrace model currently predominates the field.The results show that three of the four human cohesin core subunits (Smc1, Smc3, and Rad21) interact with themselves in an Scc3 (SA1/SA2)-dependent manner.These data support a two-ring handcuff model for the cohesin complex, which is flexible enough to establish and maintain sister chromatid cohesion as well as ensure the fidelity of chromosome segregation in higher eukaryotes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.

ABSTRACT
The cohesin complex is responsible for the accurate separation of sister chromatids into two daughter cells. Several models for the cohesin complex have been proposed, but the one-ring embrace model currently predominates the field. However, the static configuration of the embrace model is not flexible enough for cohesins to perform their functions during DNA replication, transcription, and DNA repair. We used coimmunoprecipitation, a protein fragment complement assay, and a yeast two-hybrid assay to analyze the protein-protein interactions among cohesin subunits. The results show that three of the four human cohesin core subunits (Smc1, Smc3, and Rad21) interact with themselves in an Scc3 (SA1/SA2)-dependent manner. These data support a two-ring handcuff model for the cohesin complex, which is flexible enough to establish and maintain sister chromatid cohesion as well as ensure the fidelity of chromosome segregation in higher eukaryotes.

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Handcuff model of cohesin complex. (A–C) Different configurations of two-ring models. (D) Handcuff model consists of two rings. (E) Establishment of sister chromatid cohesion. For simplicity, only cohesin complexes are shown on the model. Single-ring cohesin complexes are loaded onto the chromosomes at any stage of the cell cycle. During DNA replication at S phase, each of the rings entraps one chromatin. The handcuff is established when the two Rad21 molecules are paired and tethered either by SA1 or SA2 via interaction with the two Rad21 molecules.
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fig7: Handcuff model of cohesin complex. (A–C) Different configurations of two-ring models. (D) Handcuff model consists of two rings. (E) Establishment of sister chromatid cohesion. For simplicity, only cohesin complexes are shown on the model. Single-ring cohesin complexes are loaded onto the chromosomes at any stage of the cell cycle. During DNA replication at S phase, each of the rings entraps one chromatin. The handcuff is established when the two Rad21 molecules are paired and tethered either by SA1 or SA2 via interaction with the two Rad21 molecules.

Mentions: Although several dimeric ring models (Fig. 7, A–C) have been proposed (Campbell and Cohen-Fix, 2002; Stead et al., 2003; Huang et al., 2005; Nasmyth, 2005; Skibbens, 2005; Guacci, 2007; Skibbens et al., 2007), until now there has been no direct experimental evidence supporting these models. PCA experiments have provided two valuable clues about how Rad21 proteins interact. First, the two Rad21 molecules must have close proximity to each other in the cohesin complex. Otherwise, the YFP(NT) and YFP(CT) fragments would be unable to fold into a configuration to emit fluorescence. This close proximity prompted us to challenge the two dimeric models in which two Smc1–Smc3 heterodimers are connected by two Rad21 molecules that are on opposite sides of the ring (Fig. 7 A), or Rad21 tethers the Smc1 and Smc3 heads that belong to two different Smc1–Smc3 heterodimers (Fig. 7 B). The second clue is that the two Rad21 proteins align in an antiparallel fashion such that the YFP(NT) in YFP(NT)-Rad21 and the YFP(CT) in Rad21-YFP(CT) can be close enough to form a fluorescence-emitting configuration. These findings collectively suggest that two cohesin rings are either directly or indirectly dimerized via Rad21 subunits (Fig. 7 C).


A handcuff model for the cohesin complex.

Zhang N, Kuznetsov SG, Sharan SK, Li K, Rao PH, Pati D - J. Cell Biol. (2008)

Handcuff model of cohesin complex. (A–C) Different configurations of two-ring models. (D) Handcuff model consists of two rings. (E) Establishment of sister chromatid cohesion. For simplicity, only cohesin complexes are shown on the model. Single-ring cohesin complexes are loaded onto the chromosomes at any stage of the cell cycle. During DNA replication at S phase, each of the rings entraps one chromatin. The handcuff is established when the two Rad21 molecules are paired and tethered either by SA1 or SA2 via interaction with the two Rad21 molecules.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2600748&req=5

fig7: Handcuff model of cohesin complex. (A–C) Different configurations of two-ring models. (D) Handcuff model consists of two rings. (E) Establishment of sister chromatid cohesion. For simplicity, only cohesin complexes are shown on the model. Single-ring cohesin complexes are loaded onto the chromosomes at any stage of the cell cycle. During DNA replication at S phase, each of the rings entraps one chromatin. The handcuff is established when the two Rad21 molecules are paired and tethered either by SA1 or SA2 via interaction with the two Rad21 molecules.
Mentions: Although several dimeric ring models (Fig. 7, A–C) have been proposed (Campbell and Cohen-Fix, 2002; Stead et al., 2003; Huang et al., 2005; Nasmyth, 2005; Skibbens, 2005; Guacci, 2007; Skibbens et al., 2007), until now there has been no direct experimental evidence supporting these models. PCA experiments have provided two valuable clues about how Rad21 proteins interact. First, the two Rad21 molecules must have close proximity to each other in the cohesin complex. Otherwise, the YFP(NT) and YFP(CT) fragments would be unable to fold into a configuration to emit fluorescence. This close proximity prompted us to challenge the two dimeric models in which two Smc1–Smc3 heterodimers are connected by two Rad21 molecules that are on opposite sides of the ring (Fig. 7 A), or Rad21 tethers the Smc1 and Smc3 heads that belong to two different Smc1–Smc3 heterodimers (Fig. 7 B). The second clue is that the two Rad21 proteins align in an antiparallel fashion such that the YFP(NT) in YFP(NT)-Rad21 and the YFP(CT) in Rad21-YFP(CT) can be close enough to form a fluorescence-emitting configuration. These findings collectively suggest that two cohesin rings are either directly or indirectly dimerized via Rad21 subunits (Fig. 7 C).

Bottom Line: Several models for the cohesin complex have been proposed, but the one-ring embrace model currently predominates the field.The results show that three of the four human cohesin core subunits (Smc1, Smc3, and Rad21) interact with themselves in an Scc3 (SA1/SA2)-dependent manner.These data support a two-ring handcuff model for the cohesin complex, which is flexible enough to establish and maintain sister chromatid cohesion as well as ensure the fidelity of chromosome segregation in higher eukaryotes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.

ABSTRACT
The cohesin complex is responsible for the accurate separation of sister chromatids into two daughter cells. Several models for the cohesin complex have been proposed, but the one-ring embrace model currently predominates the field. However, the static configuration of the embrace model is not flexible enough for cohesins to perform their functions during DNA replication, transcription, and DNA repair. We used coimmunoprecipitation, a protein fragment complement assay, and a yeast two-hybrid assay to analyze the protein-protein interactions among cohesin subunits. The results show that three of the four human cohesin core subunits (Smc1, Smc3, and Rad21) interact with themselves in an Scc3 (SA1/SA2)-dependent manner. These data support a two-ring handcuff model for the cohesin complex, which is flexible enough to establish and maintain sister chromatid cohesion as well as ensure the fidelity of chromosome segregation in higher eukaryotes.

Show MeSH
Related in: MedlinePlus