Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-methylmalonyl-CoA mutase (MCM; E.C. 5,4,99,2) is the apoenzyme for catalyzing the isomerization of L-methylmalonyl-CoA to succinyl-CoA. Genetic deficiency of MCM leads to the accumulation of precursors and abnormal metabolites of L-methylmalonyl-CoA. This can be associated with fulminant metabolic acidosis, widespread secondary aberrations in systemic metabolic homeostasis, mental retardation, or even neonatal death. This disorder is termed methylmalonic acidemia (MMA). This report, describes the use of an authentic, full-length cloned human cDNA probe, MCM26, kindly provided by Dr. Fred Ledley, for Southern blot analysis of genomic DNA. The pattern of EcoRI, Sac I and Hind III restriction endonuclease sites is reported from 14 unrelated control individuals of Chinese background. A Southern blot by EcoRI to the MCM26b probe reveals invariant bands of 4.1, 3.8, and 2.2 kb respectively. By EcoRI to the MCM26c probe, 7.2 kb is invariant. By HindIII to the MCM26c probe, invariant bands are 4.8 and 2.7 kb respectively. By SacI to the MCMb probe, invariant bands are 17, 8.0, 6.0, 3.6 and 1.8 kb respectively, while the polymorphic band is at 5.6kb. When combined with more diverse samples and additional polymorphisms, this restriction fragment length polymorphism may be useful for genetic diagnostic and linkage studies of MCM in MMA.
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PMID:Restriction fragment length polymorphisms at the methylmalonyl CoA mutase locus in normal Chinese. 197 11

Many aspects of and factors required for DNA replication are conserved across all three domains of life, but there are some significant differences surrounding lagging-strand synthesis. In Archaea, a 5'-to-3' exonuclease, related to both bacterial RecJ and eukaryotic Cdc45, that associates with the replisome specifically through interactions with GINS was identified and designated GAN (for GINS-associated nuclease). Despite the presence of a well-characterized flap endonuclease (Fen1), it was hypothesized that GAN might participate in primer removal during Okazaki fragment maturation, and as a Cdc45 homologue, GAN might also be a structural component of an archaeal CMG (Cdc45, MCM, and GINS) replication complex. We demonstrate here that, individually, either Fen1 or GAN can be deleted, with no discernible effects on viability and growth. However, deletion of both Fen1 and GAN was not possible, consistent with both enzymes catalyzing the same step in primer removal from Okazaki fragments in vivo RNase HII has also been proposed to participate in primer processing during Okazaki fragment maturation. Strains with both Fen1 and RNase HII deleted grew well. GAN activity is therefore sufficient for viability in the absence of both RNase HII and Fen1, but it was not possible to construct a strain with both RNase HII and GAN deleted. Fen1 alone is therefore insufficient for viability in the absence of both RNase HII and GAN. The ability to delete GAN demonstrates that GAN is not required for the activation or stability of the archaeal MCM replicative helicase.IMPORTANCE The mechanisms used to remove primer sequences from Okazaki fragments during lagging-strand DNA replication differ in the biological domains. Bacteria use the exonuclease activity of DNA polymerase I, whereas eukaryotes and archaea encode a flap endonuclease (Fen1) that cleaves displaced primer sequences. RNase HII and the GINS-associated exonuclease GAN have also been hypothesized to assist in primer removal in Archaea Here we demonstrate that in Thermococcus kodakarensis, either Fen1 or GAN activity is sufficient for viability. Furthermore, GAN can support growth in the absence of both Fen1 and RNase HII, but Fen1 and RNase HII are required for viability in the absence of GAN.
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PMID:The GAN Exonuclease or the Flap Endonuclease Fen1 and RNase HII Are Necessary for Viability of Thermococcus kodakarensis. 2841 6

Upon replication fork arrest, the replication checkpoint kinase Cds1 is stimulated to preserve genome integrity. Robust activation of Cds1 in response to hydroxyurea prevents the endonuclease Mus81 from cleaving the stalled replication fork inappropriately. However, we find that the response is different in temperature-sensitive mcm4 mutants, affecting a subunit of the MCM replicative helicase. We show that Cds1 inhibition of Mus81 promotes genomic instability and allows mcm4-dg cells to evade cell cycle arrest. Cds1 regulation of Mus81 activity also contributes to the formation of the replication stress-induced DNA damage markers replication protein A (RPA) and Ku. These results identify a surprising role for Cds1 in driving DNA damage and disrupted chromosomal segregation under certain conditions of replication stress.
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PMID:Active Replication Checkpoint Drives Genome Instability in Fission Yeast mcm4 Mutant. 3234 Oct 83