Literature summary for 2.7.11.21 extracted from

Rawal, C.C.; Riccardo, S.; Pesenti, C.; Ferrari, M.; Marini, F.; Pellicioli, A.
Reduced kinase activity of polo kinase Cdc5 affects chromosome stability and DNA damage response in S. cerevisiae (2016), Cell Cycle, 15, 2906-2919.

Search for more literature for 2.7.11.21

Activating Compound

Activating Compound	Comment	Organism	Structure
additional information	phosphorylation of threonine residues in the T-loop of the kinase domain is pivotal for PLKs activation	Saccharomyces cerevisiae

Application

Application	Comment	Organism
diagnostics	polo-like kinases are overexpressed in several types of cancer and are a marker of bad prognosis	Saccharomyces cerevisiae

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of GFP-tagged wild-type enzyme and mutants in Saccharomyces cerevisiae strain with JKM139 background. Mutants Cdc5-T238A and Cdc5-ad variants, as well as the wild-type protein, were detectable in late S and G2/M phases, but not in late G1 and early S, mirroring the expression of the CDK1-cyclin Clb2	Saccharomyces cerevisiae

Protein Variants

Protein Variants	Comment	Organism
L251W	generation of mutant cdc5-ad that has a checkpoint adaptation defective allele, i.e. it blocks DNA damage checkpoint adaptation, cdc5-ad does not show reduced kinase activity, defective Mms4 phosphorylation and genetic interaction with sgs1DELTA	Saccharomyces cerevisiae
T238A	the substitution in the T-loop reduces the kinase activity of Cdc5. Mutant cdc5-T238A cells do not adapt to one irreparable double strand break and uncapped telomere, cdc5-T238A affects Mms4 phosphorylation and viability of sgs1D cells with alkylating agent metylmethane sulfonate	Saccharomyces cerevisiae

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
spindle	spindle pole body	Saccharomyces cerevisiae	5819	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + Mus81-Mms4 resolvase	Saccharomyces cerevisiae	-	ADP + phosphorylated Mus81-Mms4 resolvase	-	?

Organism

Organism	UniProt	Comment	Textmining
Saccharomyces cerevisiae	P32562	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
phosphoprotein	phosphorylation of threonine residues in the T-loop of the kinase domain is pivotal for PLKs activation. Phosphorylation of T238 site of Cdc5 is dispensable for cell viability	Saccharomyces cerevisiae

Source Tissue

Source Tissue	Comment	Organism	Textmining
additional information	mutants Cdc5-T238A and Cdc5-ad variants, as well as the wild-type protein, were detectable in late S and G2/M phases, but not in late G1 and early S, mirroring the expression of the CDK1-cyclin Clb2	Saccharomyces cerevisiae	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + Mus81-Mms4 resolvase	-	Saccharomyces cerevisiae	ADP + phosphorylated Mus81-Mms4 resolvase	-	?

Synonyms

Synonyms	Comment	Organism
Cdc5	-	Saccharomyces cerevisiae

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.4	-	assay at	Saccharomyces cerevisiae

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Saccharomyces cerevisiae

General Information

General Information	Comment	Organism
malfunction	reduced kinase activity of polo kinase Cdc5 affects chromosome stability and DNA damage response. Cdc5-T238A mutant cells have increased rate of chromosome loss and gross chromosomal rearrangements, indicating altered genome stability. The T238A mutation affects timely localization of Cdc5 to the spindle pole bodies and blocks cell cycle restart after one irreparable double-strand break. In cells responding to alkylating agent metylmethane sulfonate (MMS), the cdc5-T238A mutation reduces the phosphorylation of Mus81-Mms4 resolvase and exacerbates the MMS sensitivity of sgs1D cells that accumulate Holliday junctions. Rad53 dephosphorylation is severely impaired in cdc5-T238A cells till almost 20-22 hours, but the defect is less severe than in cdc5-ad mutant cells. Cdc5-T238A and Cdc5-ad mutant protein variants show altered localization to spindle pole bodies after one irreparable double strand break. Mutant phenotypes, overview	Saccharomyces cerevisiae
metabolism	the enzyme affects the Mus81-Mms4 mediated resolution pathway	Saccharomyces cerevisiae
physiological function	polo-like kinases control several aspects of eukaryotic cell division and DNA damage response. Cdc5 is the only PLK in Saccharomyces cerevisiae, it has minor effect on cell growth in unperturbed conditions. It is important of regulate Cdc5 activity through T-loop phosphorylation to preserve genome integrity and respond to DNA damage. Cdc5 may phosphorylate and regulate several factors that can suppress gross chromosomal rearrangements	Saccharomyces cerevisiae

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Release 2023.1 (January 2023)