Pds1 and Esp1
Esp1 is essential for dissolving the cohesins that hold the sister chromatids together. Esp1 activation results in proper separation of sister chromatids at anaphase (Review, Yanagida, 2000; Nasmyth et al., 2000). Pds1 binds to Esp1 and inhibits its activity (Ciosk et al., 1998).
- Initiation of anaphase requires the prior degradation of Pds1 to allow Esp1 activation (Cohen-Fix et al., 1996, Fig. 7; Visintin et al., 1997, Fig. 1).
- Pds1 inhibits Cdh1 activation, possibly by preventing Cdc14 release. Clb2 degradation in GAL-PDS1-db∆ strain is delayed for several hours (Tinker-Kulberg & Morgan, 1999; Cohen-Fix & Koshland, 1999).
- Deletion mutants of PDS1 gene are viable (Yamamoto et al., 1996).
- In response to DNA damage, Pds1 is phosphorylated (by Chk1) and becomes more stable, sister chromatid are not separated, Cdh1 is not activated, cell arrests in metaphase (Tinker-Kulberg & Morgan, 1999; Sanchez et al., 1999).
- Esp1 is a caspase, responsible for the cleavage of cohesin subunit (Scc1/Mcd1) that holds the sister chromatids together (Ciosk et al., 1998; Ciosk et al., 1998; Michaelis et al., 1997; Guacci et al., 1997).
- Esp1 is sequestered and kept inactive by Pds1. Once Pds1 is degraded, Esp1 is liberated, it initiates sister separation (Ciosk et al., 1998).
- esp1-1 is able to exit from mitosis (Clb2 degradation occurs with a 20 min delay) even though the sister chromatids are not separated Tinker-Kulberg & Morgan, 1999; Cohen-Fix & Koshland, 1999).
- Esp1 is an element of the FEAR pathway and therefore plays a role in early release of Cdc14 (Stegmeier et al., 2002)
Level and regulation::
- Pds1 transcription peaks at G1/S (Spellman et al., 1998); protein peaks at M phase (Tinker-Kulberg & Morgan, 1999).
- Pds1 degradation at anaphase which requires Cdc20 (Yamamoto et al., 1996).
- If ectopically expressed (Prinz et al., 1998), Pds1 is unstable in G1, with a half-life <15 min and its degradation depends on Cdh1 (Rudner et al., 2000a). It is stable in S, G2 or M phase with a half-life >60 min.
- Esp1 transcription is constant throughout the cell cycle (Spellman et al., 1998).
- Esp1 is found in the nucleus during the metaphase-anaphase transition, partly bound to the spindles (Ciosk et al., 1998).
- Cdc5 phosphorylation of Scc1 strongly enhances its cleavage by Esp1 (Alexandru et al., 2001).