Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Generation of meiotic crossovers in many eukaryotes requires the elimination of anti-crossover activities by using the Msh4-Msh5 heterodimer to block helicases. Msh4 and Msh5 have been lost from the flies Drosophila and Glossina, but we identified a complex of minichromosome maintenance (MCM) proteins that functionally replace Msh4-Msh5. We found that REC, an ortholog of MCM8 that evolved under strong positive selection in flies, interacts with MEI-217 and MEI-218, which arose from a previously undescribed metazoan-specific MCM protein. Meiotic crossovers were reduced in Drosophila rec, mei-217, and mei-218 mutants; however, removal of the Bloom syndrome helicase (BLM) ortholog restored crossovers. Thus, MCMs were co-opted into a novel complex that replaced the meiotic pro-crossover function of Msh4-Msh5 in flies.
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PMID:Evolution of an MCM complex in flies that promotes meiotic crossovers by blocking BLM helicase. 2322 58

The ability to restart broken DNA replication forks is essential across all domains of life. In Escherichia coli, the priA, priB, priC, and dnaT genes encode the replication restart proteins (RRPs) to accomplish this task. PriA plays a critical role in replication restart such that its absence reveals a dramatic phenotype: poor growth, high basal levels of SOS expression, poorly partitioned nucleoids (Par-), UV sensitivity, and recombination deficiency (Rec-). PriA has 733 amino acids, and its structure is composed of six domains that enable it to bind to DNA replication fork-like structures, remodel the strands of DNA, interact with SSB (single-stranded DNA binding protein), PriB, and DnaT, and display ATPase, helicase, and translocase activities. We have characterized a new priA mutation called priA316::cat It is a composite mutation involving an insertion that truncates the protein within the winged-helix domain (at the 154th codon) and an ACG (Thr)-to-ATG (Met) mutation that allows reinitiation of translation at the 157th codon such that PriA is expressed in two pieces. priA316::cat phenotypes are like those of the wild type for growth, recombination, and UV resistance, revealing only a slightly increased level of SOS expression and defects in nucleoid partitioning in the mutant. Both parts of PriA are required for activity, and the N-terminal fragment can be optimized to yield wild-type activity. A deletion of the lon protease suppresses priA316::cat phenotypes. We hypothesize the two parts of PriA form a complex that supplies most of the PriA activity needed in the cell.IMPORTANCE PriA is a highly conserved multifunctional protein that plays a crucial role in the essential process of replication restart. Here we characterize an insertion mutation of priA with an intragenic suppressor such that it is now made in two parts. These two pieces split the winged-helix domain to separate the N-terminal 3' DNA-binding domain from the C-terminal domain of PriA. It is hypothesized that the two pieces form a complex that is capable of almost wild type priA function. The composite mutation leads to a moderate level of SOS expression and defects in partitioning of the chromosomes. Full function is restored by deletion of lon, suggesting that stability of this complex may be a reason for the partial phenotypes seen.
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PMID:A priA Mutant Expressed in Two Pieces Has Almost Full Activity in Escherichia coli K-12. 2860 60

ATP-dependent chromatin remodeling proteins use the energy released from ATP hydrolysis to reposition nucleosomes in DNA-dependent processes. These proteins are classified as SF2 helicases. SMARCAL1, a member of this protein family, is known to modulate both DNA repair and transcription by specifically recognizing DNA molecules possessing double-strand to single-strand transition regions. Mutations in this gene cause a rare autosomal recessive disorder known as Schimke Immuno-Osseous Dysplasia (SIOD).Structural studies have shown that the ATP-dependent chromatin remodeling proteins possess two RecA-like domains termed as RecA-like domain 1 and RecA-like domain 2. Using Active DNA-dependent ATPase A domain (ADAAD), the bovine homolog of SMARCAL1, as a model system we had previously shown that the RecA-like domain 1 containing helicase motifs Q, I, Ia, II, and III are sufficient for ligand binding; however, the Rec A-like domain 2 containing motifs IV, V, and VI are needed for ATP hydrolysis. In the present study, we have focused on the motifs present in the RecA-like domain 2. Our studies demonstrate that the presence of an aromatic residue in motif IV is needed for interaction with DNA in the presence of ATP. We also show that the motif V is required for the catalytic efficiency of the protein and motif VI is needed for interaction with DNA in the presence of ATP. Finally, we show that the SIOD-associated mutation, R820H, present in motif VI results in loss of ATPase activity, and therefore, reduced response to DNA damage.
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PMID:RecA-like domain 2 of DNA-dependent ATPase A domain, a SWI2/SNF2 protein, mediates conformational integrity and ATP hydrolysis. 2974 40


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