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Recombination protein Tid1p controls resolution of cohesin-dependent linkages in meiosis in Saccharomyces cerevisiae.

Kateneva AV, Konovchenko AA, Guacci V, Dresser ME - J. Cell Biol. (2005)

Bottom Line: Genetic results indicate that the primary defect in these cells is a failure to resolve Mcd1p-mediated connections.Tid1p interacts with recombination enzymes Dmc1p and Rad51p and has an established role in recombination repair.We propose that Tid1p remodels Mcd1p-mediated cohesion early in meiotic prophase to facilitate interhomologue recombination and the subsequent segregation of homologous chromosomes.

View Article: PubMed Central - PubMed

Affiliation: Program in Molecular, Cell, and Developmental Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.

ABSTRACT
Sister chromatid cohesion and interhomologue recombination are coordinated to promote the segregation of homologous chromosomes instead of sister chromatids at the first meiotic division. During meiotic prophase in Saccharomyces cerevisiae, the meiosis-specific cohesin Rec8p localizes along chromosome axes and mediates most of the cohesion. The mitotic cohesin Mcd1p/Scc1p localizes to discrete spots along chromosome arms, and its function is not clear. In cells lacking Tid1p, which is a member of the SWI2/SNF2 family of helicase-like proteins that are involved in chromatin remodeling, Mcd1p and Rec8p persist abnormally through both meiotic divisions, and chromosome segregation fails in the majority of cells. Genetic results indicate that the primary defect in these cells is a failure to resolve Mcd1p-mediated connections. Tid1p interacts with recombination enzymes Dmc1p and Rad51p and has an established role in recombination repair. We propose that Tid1p remodels Mcd1p-mediated cohesion early in meiotic prophase to facilitate interhomologue recombination and the subsequent segregation of homologous chromosomes.

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Model of Tid1p regulation of sister chromatid cohesion. Black and gray lines represent chromatids; black ovals represent centromeres. Dark gray spheres represent Mcd1p-dependent sister chromatid connections, and light gray spheres represent Rec8p-dependent connections. Spheres marked with black “hats” represent connections that are resistant to separase cleavage. Black arrows represent pulling forces of the spindle. Boxes indicate areas enlarged in the model. (1) Loading of Mcd1p occurs at a location that is permissive for DSBs. (2) Loading of additional factors marks the site for interhomologue recombination and renders Mcd1p and nearby Rec8p resistant to separase cleavage. (3) Remodeling/removal of cohesins by Tid1p results in local sister separation in an environment that promotes interaction of the broken chromatid with the homologue during repair. (4) In the absence of Tid1p, the loading of factors determining the fate of DSBs occurs normally, but local cohesion is not resolved, simultaneously creating an impediment for repair and persistent connections. Eventual inefficient dislodging of cohesins (for example, during resection or by Rad54p) allows the completion of recombination and results in a number of chiasmata that are flanked by areas of separase-resistant cohesion (or, in the absence of a DSB, separase-resistant connections alone). According to this model, the remodeling function of Tid1p in prophase would be promoted by but not dependent on DSB metabolism.
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fig9: Model of Tid1p regulation of sister chromatid cohesion. Black and gray lines represent chromatids; black ovals represent centromeres. Dark gray spheres represent Mcd1p-dependent sister chromatid connections, and light gray spheres represent Rec8p-dependent connections. Spheres marked with black “hats” represent connections that are resistant to separase cleavage. Black arrows represent pulling forces of the spindle. Boxes indicate areas enlarged in the model. (1) Loading of Mcd1p occurs at a location that is permissive for DSBs. (2) Loading of additional factors marks the site for interhomologue recombination and renders Mcd1p and nearby Rec8p resistant to separase cleavage. (3) Remodeling/removal of cohesins by Tid1p results in local sister separation in an environment that promotes interaction of the broken chromatid with the homologue during repair. (4) In the absence of Tid1p, the loading of factors determining the fate of DSBs occurs normally, but local cohesion is not resolved, simultaneously creating an impediment for repair and persistent connections. Eventual inefficient dislodging of cohesins (for example, during resection or by Rad54p) allows the completion of recombination and results in a number of chiasmata that are flanked by areas of separase-resistant cohesion (or, in the absence of a DSB, separase-resistant connections alone). According to this model, the remodeling function of Tid1p in prophase would be promoted by but not dependent on DSB metabolism.

Mentions: We propose that Tid1p remodels Mcd1p-mediated cohesion to promote and regulate interhomologue recombination (Fig. 9). In this model, domains of Mcd1p would colocalize with DSBs that initiate meiotic recombination (and may be hot spots for DSBs; Petes, 2001). These domains would initially be prohibitive for impending interhomologue recombination for the following reason. In mitosis, cohesion between sister chromatids that was established during replication and de novo loading of cohesins at a DSB site are required for postreplicative DSB repair (Sjogren and Nasmyth, 2001; Strom et al., 2004; Unal et al., 2004). One of the roles proposed for cohesins in postreplicative repair in mitotic cells is to keep sister chromatids in proximity (Strom et al., 2004; Unal et al., 2004). If so, then in meiosis, additional factors would have to be incorporated at the Mcd1p domains to guide DSB repair to lead to the separation of, rather than the alignment of, sister chromatids. We suggest that Tid1p specifically facilitates this separation, which allows interaction with one of the chromatids of the homologue, perhaps by promoting displacement from the loop to the axis (Blat et al., 2002). In the absence of this loop displacement, the DSB ends would be free to separate and could give rise to the separation of Dmc1p and Rad51p foci that were reported for tid1Δ (Shinohara et al., 2000). This two-step mechanism for control over the fate of multiple programmed DSBs in meiosis would provide an escape route through sister-based repair in case of a failure to initiate repair involving the homologue as a template. Remodeling of cohesins by Tid1p could be promoted by Tid1p interaction with Dmc1p, which is required for the interhomologue bias of recombination in meiosis (Bishop et al., 1992; Dresser et al., 1997). Thus, Tid1p would serve to remodel chromosome structure, which is promoted by but is not necessarily dependent on DSB metabolism. The model predicts that Mcd1p and proteins involved in DSB repair should colocalize to some degree depending on their relative times of activity and on whether Mcd1p is involved at all or at a subset of DSB sites.


Recombination protein Tid1p controls resolution of cohesin-dependent linkages in meiosis in Saccharomyces cerevisiae.

Kateneva AV, Konovchenko AA, Guacci V, Dresser ME - J. Cell Biol. (2005)

Model of Tid1p regulation of sister chromatid cohesion. Black and gray lines represent chromatids; black ovals represent centromeres. Dark gray spheres represent Mcd1p-dependent sister chromatid connections, and light gray spheres represent Rec8p-dependent connections. Spheres marked with black “hats” represent connections that are resistant to separase cleavage. Black arrows represent pulling forces of the spindle. Boxes indicate areas enlarged in the model. (1) Loading of Mcd1p occurs at a location that is permissive for DSBs. (2) Loading of additional factors marks the site for interhomologue recombination and renders Mcd1p and nearby Rec8p resistant to separase cleavage. (3) Remodeling/removal of cohesins by Tid1p results in local sister separation in an environment that promotes interaction of the broken chromatid with the homologue during repair. (4) In the absence of Tid1p, the loading of factors determining the fate of DSBs occurs normally, but local cohesion is not resolved, simultaneously creating an impediment for repair and persistent connections. Eventual inefficient dislodging of cohesins (for example, during resection or by Rad54p) allows the completion of recombination and results in a number of chiasmata that are flanked by areas of separase-resistant cohesion (or, in the absence of a DSB, separase-resistant connections alone). According to this model, the remodeling function of Tid1p in prophase would be promoted by but not dependent on DSB metabolism.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171180&req=5

fig9: Model of Tid1p regulation of sister chromatid cohesion. Black and gray lines represent chromatids; black ovals represent centromeres. Dark gray spheres represent Mcd1p-dependent sister chromatid connections, and light gray spheres represent Rec8p-dependent connections. Spheres marked with black “hats” represent connections that are resistant to separase cleavage. Black arrows represent pulling forces of the spindle. Boxes indicate areas enlarged in the model. (1) Loading of Mcd1p occurs at a location that is permissive for DSBs. (2) Loading of additional factors marks the site for interhomologue recombination and renders Mcd1p and nearby Rec8p resistant to separase cleavage. (3) Remodeling/removal of cohesins by Tid1p results in local sister separation in an environment that promotes interaction of the broken chromatid with the homologue during repair. (4) In the absence of Tid1p, the loading of factors determining the fate of DSBs occurs normally, but local cohesion is not resolved, simultaneously creating an impediment for repair and persistent connections. Eventual inefficient dislodging of cohesins (for example, during resection or by Rad54p) allows the completion of recombination and results in a number of chiasmata that are flanked by areas of separase-resistant cohesion (or, in the absence of a DSB, separase-resistant connections alone). According to this model, the remodeling function of Tid1p in prophase would be promoted by but not dependent on DSB metabolism.
Mentions: We propose that Tid1p remodels Mcd1p-mediated cohesion to promote and regulate interhomologue recombination (Fig. 9). In this model, domains of Mcd1p would colocalize with DSBs that initiate meiotic recombination (and may be hot spots for DSBs; Petes, 2001). These domains would initially be prohibitive for impending interhomologue recombination for the following reason. In mitosis, cohesion between sister chromatids that was established during replication and de novo loading of cohesins at a DSB site are required for postreplicative DSB repair (Sjogren and Nasmyth, 2001; Strom et al., 2004; Unal et al., 2004). One of the roles proposed for cohesins in postreplicative repair in mitotic cells is to keep sister chromatids in proximity (Strom et al., 2004; Unal et al., 2004). If so, then in meiosis, additional factors would have to be incorporated at the Mcd1p domains to guide DSB repair to lead to the separation of, rather than the alignment of, sister chromatids. We suggest that Tid1p specifically facilitates this separation, which allows interaction with one of the chromatids of the homologue, perhaps by promoting displacement from the loop to the axis (Blat et al., 2002). In the absence of this loop displacement, the DSB ends would be free to separate and could give rise to the separation of Dmc1p and Rad51p foci that were reported for tid1Δ (Shinohara et al., 2000). This two-step mechanism for control over the fate of multiple programmed DSBs in meiosis would provide an escape route through sister-based repair in case of a failure to initiate repair involving the homologue as a template. Remodeling of cohesins by Tid1p could be promoted by Tid1p interaction with Dmc1p, which is required for the interhomologue bias of recombination in meiosis (Bishop et al., 1992; Dresser et al., 1997). Thus, Tid1p would serve to remodel chromosome structure, which is promoted by but is not necessarily dependent on DSB metabolism. The model predicts that Mcd1p and proteins involved in DSB repair should colocalize to some degree depending on their relative times of activity and on whether Mcd1p is involved at all or at a subset of DSB sites.

Bottom Line: Genetic results indicate that the primary defect in these cells is a failure to resolve Mcd1p-mediated connections.Tid1p interacts with recombination enzymes Dmc1p and Rad51p and has an established role in recombination repair.We propose that Tid1p remodels Mcd1p-mediated cohesion early in meiotic prophase to facilitate interhomologue recombination and the subsequent segregation of homologous chromosomes.

View Article: PubMed Central - PubMed

Affiliation: Program in Molecular, Cell, and Developmental Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.

ABSTRACT
Sister chromatid cohesion and interhomologue recombination are coordinated to promote the segregation of homologous chromosomes instead of sister chromatids at the first meiotic division. During meiotic prophase in Saccharomyces cerevisiae, the meiosis-specific cohesin Rec8p localizes along chromosome axes and mediates most of the cohesion. The mitotic cohesin Mcd1p/Scc1p localizes to discrete spots along chromosome arms, and its function is not clear. In cells lacking Tid1p, which is a member of the SWI2/SNF2 family of helicase-like proteins that are involved in chromatin remodeling, Mcd1p and Rec8p persist abnormally through both meiotic divisions, and chromosome segregation fails in the majority of cells. Genetic results indicate that the primary defect in these cells is a failure to resolve Mcd1p-mediated connections. Tid1p interacts with recombination enzymes Dmc1p and Rad51p and has an established role in recombination repair. We propose that Tid1p remodels Mcd1p-mediated cohesion early in meiotic prophase to facilitate interhomologue recombination and the subsequent segregation of homologous chromosomes.

Show MeSH
Related in: MedlinePlus