In yeast, the initiation of telomere replication at the late S phase involves in combined actions of kinases on Cdc13, the telomere binding protein. Cdc13 recruits telomerase to telomeres through its interaction with Est1, a component of telomerase. However, how cells terminate the function of telomerase at G2/M is still elusive. Here we show that the protein phosphatase 2A (PP2A) subunit Pph22 and the yeast Aurora kinase homologue Ipl1 coordinately inhibit telomerase at G2/M by dephosphorylating and phosphorylating the telomerase recruitment domain of Cdc13, respectively. While Pph22 removes Tel1/Mec1-mediated Cdc13 phosphorylation to reduce Cdc13-Est1 interaction, Ipl1-dependent Cdc13 phosphorylation elicits dissociation of Est1-TLC1, the template RNA component of telomerase. Failure of these regulations prevents telomerase from departing telomeres, causing perturbed telomere lengthening and prolonged M phase. Together our results demonstrate that differential and additive actions of PP2A and Aurora on Cdc13 limit telomerase action by removing active telomerase from telomeres at G2/M phase.
Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.
| Gene/Complex | Qualifier | Gene Ontology Term | Annotation Extension | Evidence | Source | Assigned On |
|---|---|---|---|---|---|---|
| PPH22 | enables | protein serine/threonine phosphatase activity | has input CDC13 | IDA | SGD | 2021-11-16 |
| PPH22 | is active in | chromosome, telomeric region | IMP | SGD | 2021-11-16 | |
| PPH22 | involved in | negative regulation of ribonucleoprotein complex localization | part of G2/M transition of mitotic cell cycle, occurs in chromosome, telomeric region | IMP | SGD | 2021-11-16 |
| PPH22 | involved in | G2/M transition of mitotic cell cycle | IMP | SGD | 2024-03-22 | |
| CDC13 | involved in | ribonucleoprotein complex localization | happens during mitotic S phase, has input telomerase holoenzyme complex | IMP | SGD | 2021-11-16 |
| IPL1 | enables | protein kinase activity | has input CDC13 | IDA | SGD | 2021-11-16 |
Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.
| Gene | Phenotype | Experiment Type | Mutant Information | Strain Background | Chemical | Details |
|---|---|---|---|---|---|---|
| PPH22 | protein/peptide distribution: abnormal Reporter: Est1p | classical genetics | null Allele: pph22-Δ | S288C | Details: delayed departure of Est1p from telomeres | |
| CDC13 | protein/peptide distribution: abnormal Reporter: Est1p | classical genetics | unspecified Allele: cdc13-S255A S255A; TEL1/MEC1 phosphorylation site and telomerase recruitment domain mutated | S288C | Details: recruitment of Est1p to telomeres in S phase is decreased | |
| PPH22 | protein/peptide distribution: abnormal Reporter: Est2p | classical genetics | null Allele: pph22-Δ | S288C | Details: delayed departure of Est2p from telomeres | |
| CDC13 | protein/peptide distribution: abnormal Reporter: Est2p | classical genetics | unspecified Allele: cdc13-S255A S255A; TEL1/MEC1 phosphorylation site and telomerase recruitment domain mutated | S288C | Details: recruitment of Est2p to telomeres in S phase is decreased | |
| CDC13 | protein/peptide distribution: abnormal Reporter: Est2p | classical genetics | unspecified Allele: cdc13-S314A S314A; IPL1 phosphorylation site and telomerase recruitment domain mutated | S288C | Details: delayed departure of Est2p from telomeres | |
| TEL1 | protein/peptide modification: decreased Reporter: Cdc13p | classical genetics | null Allele: tel1-Δ | S288C | nocodazole | Details: decreased phosphorylation of Cdc13p at S249 and/or S255 (telomerase recruitment domain) during the G2/M phase transition in nocodazole arrested cells |
| MEC1 | protein/peptide modification: decreased Reporter: Cdc13p | classical genetics | null Allele: mec1-Δ | S288C | nocodazole | Details: decreased phosphorylation of Cdc13p at S249 and/or S255 (telomerase recruitment domain) during the G2/M phase transition in nocodazole arrested cells |
| IPL1 | protein/peptide modification: decreased Reporter: Cdc13p | classical genetics | conditional Allele: ipl1-4 | Other | nocodazole | Details: large decrease in the phosphorylation of Cdc13p at S314 during the the G2/M phase transition in nocodazole arrested cells |
| PPH22 | protein/peptide modification: increased Reporter: Cdc13p | classical genetics | null Allele: pph22-Δ | S288C | nocodazole | Details: increased phosphorylation of Cdc13p at S249 and/or S255 (telomerase recruitment domain) during the G2/M phase transition in nocodazole arrested cells |
| CDC13 | telomere length: decreased | classical genetics | unspecified Allele: cdc13-S255A S255A; TEL1/MEC1 phosphorylation site and telomerase recruitment domain mutated | S288C |
Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, or SPELL.
Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.
| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
|---|
Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.
| Interactor | Interactor | Assay | Annotation | Action | Modification | |
|---|---|---|---|---|---|---|
| CDC13 | PPH3 | Biochemical Activity | manually curated | Hit-Bait | Dephosphorylation | |
| CDC13 | EST1 | Affinity Capture-Western | manually curated | Hit-Bait | No Modification | |
| CDC13 | IPL1 | Biochemical Activity | manually curated | Hit-Bait | phosphorylated residue | |
| CDC13 | TLC1 | Affinity Capture-RNA | manually curated | Bait-Hit | No Modification | |
| EST1 | TLC1 | Affinity Capture-RNA | manually curated | Bait-Hit | No Modification | |
| EST2 | TLC1 | Affinity Capture-RNA | manually curated | Bait-Hit | No Modification | |
| PPH21 | CDC13 | Biochemical Activity | manually curated | Bait-Hit | Dephosphorylation | |
| PPH22 | CDC13 | Biochemical Activity | manually curated | Bait-Hit | Dephosphorylation |