High impact information on MEC3

• Finally, deletion of MEC3 results in telomere elongation, whereas cells with deletions of both SET1 and MEC3 do not have elongated telomeres [1].
• An assay that measures DNA damage processing in vivo showed that the checkpoint genes RAD17, RAD24, and MEC3 activated an exonuclease that degrades DNA [2].
• Loss of Stn1 function activated the RAD9 and MEC3 G2/M checkpoints, therefore confirming that DNA damage is generated [3].
• A structural model of the UNC-86 POU domain, including base pairs and amino acid residues required for MEC-3 interaction, revealed that P145 and L195 are part of a hydrophobic pocket which is similar to the OCA-B-binding domain of the mammalian POU protein, Oct-1 [4].
• We demonstrate that Ddc1p interacts physically in vivo with Mec3p, and this interaction requires Rad17p [5].

Biological context of MEC3

• Mec1p is essential for phosphorylation of the yeast DNA damage checkpoint protein Ddc1p, which physically interacts with Mec3p [5].
• Role of a complex containing Rad17, Mec3, and Ddc1 in the yeast DNA damage checkpoint pathway [6].
• The amino terminus of Rad17 is required for its interaction with Mec3, and the protein encoded by the rad17-1 allele, containing a missense mutation at the amino terminus, is defective for its interaction with Mec3 in vivo [6].
• Our findings indicate that interactions between SET1 and MEC3 have a role in DNA repair and telomere function [1].
• Although RAD17, RAD24 and MEC3 are not required for cell cycle arrest when S phase is inhibited by hydroxyurea (HU), they do contribute to the viability of yeast cells grown in the presence of HU, possibly because they are required for the repair of HU-induced DNA damage [7].

Anatomical context of MEC3

• In yeast producing PIP3, PKB/c-Akt localizes to the plasma membrane and its phosphorylation is enhanced [8].

Associations of MEC3 with chemical compounds

• We have cloned and characterized the gene of one complementation group, PIP3, whose product is necessary both for delaying entry into S phase or mitosis when cells are UV irradiated in G1 or G2 phase and for lowering the rate of ongoing DNA synthesis in the presence of methyl methanesulfonate [9].
• Growth arrest by PI3K correlates with loss of PIP2 (phosphatidylinositol 4,5-bisphosphate) and its conversion into PIP3 (phosphatidylinositol 3,4,5-trisphosphate) [8].

Physical interactions of MEC3

• Function of Rad17/Mec3/Ddc1 and its partial complexes in the DNA damage checkpoint [10].

Other interactions of MEC3

• On the other hand, Rad24 is not found to associate with Rad17, Mec3, and Ddc1 [6].
• A dominant-negative MEC3 mutant uncovers new functions for the Rad17 complex and Tel1 [11].
• The DDC1 gene was identified, together with MEC3 and other checkpoint genes, during a screening for mutations causing synthetic lethality when combined with a conditional allele altering DNA primase [12].
• Its known interactions with the checkpoint proteins Mec3p and Ddc1p in a PCNA-like complex indicate a sensor role in damage recognition [13].
• In this work, we demonstrate both an in vivo and in vitro physical interaction between the Mec3 and Ddc1 subunits of the 9-1-1 clamp and the Rev7 subunit of the Polzeta TLS polymerase [14].

Analytical, diagnostic and therapeutic context of MEC3

• Molecular cloning via the reverse genetics complementation approach using a yeast genomic library suggested pso9-1 to be a mutant allele of the DNA damage checkpoint control gene MEC3 [15].

References