Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.5.1.2 (DNA ligase)
 2,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel nucleolar component has been identified and cloned using a human autoimmune serum. This antigen, as inferred from the cDNA sequence, is an Mr 55000 protein. Immuno blot analysis, however, of both the native protein and the in vitro translation products of the cDNA showed that they migrate on SDS-PAGE at an apparent molecular mass of 90000 A BLAST search using the cDNA sequence indicated that it is in an antisense orientation to and overlaps the gene of the DNA repair enzyme ERCC-1. An open reading frame, without a translational start site, had been observed by others in this region of the chromosome 19 (19q13.3) and the putative protein was termed ASE-1 (Anti-Sense to ERCC-1). Our cDNA is a full-length equivalent of that open reading frame. ASE-1 was found to contain two domains that are present in a number of nucleolar specific proteins originating from a variety of organisms: a glycine-, arginine- and phenylalanine-rich putative nucleotide interaction domain and an alternating basic/acidic region. Indirect immunofluorescence analysis using antibodies generated to cloned regions of ASE-1 indicated that this protein occurs at the fibrillar centres of the nucleolus in interphase, the putative sites of rDNA transcription, and during cell division it is localized to the nucleolus organizer regions of the chromosomes. ASE-1 co-localises with the RNA polymerase I transcription initiation factor UBF/NOR-90 throughout all stages of the cell cycle and these two proteins associate with each other in vitro.
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PMID:ASE-1: a novel protein of the fibrillar centres of the nucleolus and nucleolus organizer region of mitotic chromosomes. 942 81

The Saccharomyces cerevisiae high mobility group protein HMO1 has two DNA binding domains, box A and box B, and a lysine-rich C-terminal extension. Among other functions, HMO1 has been implicated as a component of the RNA polymerase I transcription machinery. We report here that HMO1 promotes DNA apposition as evidenced by its stimulation of end-joining in the presence of T4 DNA ligase. Analysis of truncated HMO1 variants shows that enhanced DNA end-joining requires the C-terminal domain but that box A is dispensable. The efficiency of joining DNA ends with different nucleotide content parallels that of DNA ligase, and optimal ligation efficiency is attained when DNA is effectively saturated with protein, implying that HMO1 binds internal sites in preference to DNA ends. Removal of the C-terminal tail does not attenuate the self-association characteristic of HMO1 but alters the stoichiometry of binding and prevents intramolecular DNA cyclization. This suggests that the C-terminal domain mediates an accretion of HMO1 on DNA that causes in-phase DNA bending and that binding of HMO1 lacking the C-terminal domain results in out-of-phase bending. Taken together, our results show that HMO1 shares with mammalian HMGB proteins the ability to promote DNA association. Notably, the C-terminal domain mediates both DNA end-joining and an accretion of multiple HMO1 protomers on duplex DNA that produces in-phase DNA bending. This mode of binding is reminiscent of that proposed for the mammalian RNA polymerase I transcription factor UBF.
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PMID:The C-terminal domain of yeast high mobility group protein HMO1 mediates lateral protein accretion and in-phase DNA bending. 2040 81