Dataset Information

Down-regulation of tricarboxylic acid (TCA) cycle genes blocks progression through the first mitotic division in Caenorhabditis elegans embryos.

ABSTRACT: The cell cycle is a highly regulated process that enables the accurate transmission of chromosomes to daughter cells. Here we uncover a previously unknown link between the tricarboxylic acid (TCA) cycle and cell cycle progression in the Caenorhabditis elegans early embryo. We found that down-regulation of TCA cycle components, including citrate synthase, malate dehydrogenase, and aconitase, resulted in a one-cell stage arrest before entry into mitosis: pronuclear meeting occurred normally, but nuclear envelope breakdown, centrosome separation, and chromosome condensation did not take place. Mitotic entry is controlled by the cyclin B-cyclin-dependent kinase 1 (Cdk1) complex, and the inhibitory phosphorylation of Cdk1 must be removed in order for the complex to be active. We found that following down-regulation of the TCA cycle, cyclin B levels were normal but CDK-1 remained inhibitory-phosphorylated in one-cell stage-arrested embryos, indicative of a G2-like arrest. Moreover, this was not due to an indirect effect caused by checkpoint activation by DNA damage or replication defects. These observations suggest that CDK-1 activation in the C. elegans one-cell embryo is sensitive to the metabolic state of the cell, and that down-regulation of the TCA cycle prevents the removal of CDK-1 inhibitory phosphorylation. The TCA cycle was previously shown to be necessary for the development of the early embryo in mammals, but the molecular processes affected were not known. Our study demonstrates a link between the TCA cycle and a specific cell cycle transition in the one-cell stage embryo.

SUBMITTER: Rahman MM

PROVIDER: S-EPMC3932911 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Accurate identification of synteny blocks is an important step in comparative genomics towards the understanding of genome architecture and expression. Most computer programs developed in the last decade for identifying synteny blocks have limitations. To address these limitations, we recently developed a robust program called OrthoCluster, and an online database OrthoClusterDB. In this work, we have demonstrated the application of OrthoCluster in identifying synteny blocks between the genomes of Caenorhabditis elegans and Caenorhabditis briggsae, two closely related hermaphrodite nematodes.Initial identification and analysis of synteny blocks using OrthoCluster enabled us to systematically improve the genome annotation of C. elegans and C. briggsae, identifying 52 potential novel genes in C. elegans, 582 in C. briggsae, and 949 novel orthologous relationships between these two species. Using the improved annotation, we have detected 3,058 perfect synteny blocks that contain no mismatches between C. elegans and C. briggsae. Among these synteny blocks, the majority are mapped to homologous chromosomes, as previously reported. The largest perfect synteny block contains 42 genes, which spans 201.2 kb in Chromosome V of C. elegans. On average, perfect synteny blocks span 18.8 kb in length. When some mismatches (interruptions) are allowed, synteny blocks ("imperfect synteny blocks") that are much larger in size are identified. We have shown that the majority (80%) of the C. elegans and C. briggsae genomes are covered by imperfect synteny blocks. The largest imperfect synteny block spans 6.14 Mb in Chromosome X of C. elegans and there are 11 synteny blocks that are larger than 1 Mb in size. On average, imperfect synteny blocks span 63.6 kb in length, larger than previously reported.We have demonstrated that OrthoCluster can be used to accurately identify synteny blocks and have found that synteny blocks between C. elegans and C. briggsae are almost three-folds larger than previously identified.

Dataset Information

Down-regulation of tricarboxylic acid (TCA) cycle genes blocks progression through the first mitotic division in Caenorhabditis elegans embryos.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets