Academic journal article Genetics

Pds1p Is Required for Meiotic Recombination and Prophase I Progression in Saccharomyces Cerevisiae

Academic journal article Genetics

Pds1p Is Required for Meiotic Recombination and Prophase I Progression in Saccharomyces Cerevisiae

Article excerpt

ABSTRACT

Sister-chromatid separation at the metaphase-anaphase transition is regulated by a proteolytic cascade. Destruction of the securin Pds1p liberates the Esp1p separase, which ultimately targets the mitotic cohesin Mcd1p/Scc1p for destruction. Pds1p stabilization by the spindle or DNA damage checkpoints prevents sister-chromatid separation while mutants lacking PDS1 (pds1Δ) are temperature sensitive for growth due to elevated chromosome loss. This report examined the role of the budding yeast Pds1p in meiotic progression using genetic, cytological, and biochemical assays. Similar to its mitotic function, Pds1p destruction is required for metaphase I-anaphase I transition. However, even at the permissive temperature for growth, pds1Δ mutants arrest with prophase I spindle and nuclear characteristics. This arrest was partially suppressed by preventing recombination initiation or by inactivating a subset of recombination checkpoint components. Further studies revealed that Pds1p is required for recombination in both double-strand-break formation and synaptonemal complex assembly. Although deleting PDS1 did not affect the degradation of the meiotic cohesin Rec8p, Mcd1p was precociously destroyed as cells entered the meiotic program. This role is meiosis specific as Mcd1p destruction is not altered in vegetative pds1Δ cultures. These results define a previously undescribed role for Pds1p in cohesin maintenance, recombination, and meiotic progression.

MEIOSIS generates haploid gametes through a specialized cell division process that consists of one round of DNA replication followed by two nuclear divisions. The first meiotic division is unique to meiosis for two reasons. First, during the extended prophase I, homologous chromosomes synapse and undergo high levels of genetic recombination that is essential for the correct chromosome alignment at metaphase I (KUPIEC et al. 1997). Second, following resolution of the recombination intermediates, the spindle makes monopolar attachments to the sister chromatids permitting the execution of meiosis I or the reductional division. Meiosis II resembles mitosis in that the replicated sister chromatids segregate to opposite poles.

Meiotic recombination establishes chromosome alignment essential for accurate segregation during the first meiotic division. It follows therefore that the first step in this process, i.e., the formation of doublestrand breaks (DSBs), is also a critical event (Keeney et al. 1997). To date, in budding yeast, at least 10 proteins are required for this process (reviewed in BAUDAT AND KEENEY 2001; ARORA et al. 2004; BORDE 2007). Some of these proteins are meiosis specific whereas others also have roles in mitotically dividing cells. Significantly, apart from Spo11p, which initiates DSB formation (KEENEY et al. 1997), little is known about the biochemical function of the individual components of this complex and how they are regulated.

The proper execution of recombination and other meiotic landmark events is governed by several checkpoint pathways (reviewed in ROEDER 1997). The DNA damage checkpoint senses broken DNA ends and transduces the signal through the Rad9p kinase (WEBER AND BYERS 1992; LYDALL et al. 1996). The meiotic recombination checkpoint is more complex and can be divided into three different pathways depending on the signal that is generated (reviewed in ROEDER AND BAILIS 2000; HOCHWAGEN and AMON 2006). The rad50S checkpoint is triggered by unprocessed DSBs generated by the endonuclease Spo11p. The recombination (or dmc1) pathway is activated by resected, but not processed, DSB ends. Finally, the Zip1 checkpoint functions following strand invasion and is activated by an as-yetundefined signal. Although the different checkpoint pathways monitor different steps in the recombination process, they share many components. For example, the various recombination DNA lesions are recognized by the Rad17-Ddc1-Mec3 clamp loader. However, different proteins are recruited depending on the checkpoint signal. …

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