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Query: EC:6.5.1.2 (DNA ligase)
 2,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular mechanism by which poly(ADP-ribose) participates in DNA repair was investigated using purified DNA ligase in DNA-histone systems. The ligase activity was markedly inhibited by histones; the inhibition was greater than 80% with histone H1 at concentrations equal to DNA. This inhibition was reversed efficiently by poly(ADP-ribose), either added exogenously or synthesized in situ with poly(ADP-ribose) synthetase. The reversal effect was specific for poly(ADP-ribose); other polyanions such as mRNA, rRNA's, tRNA, and synthetic poly(A) were less effective or totally ineffective. The poly(ADP-ribose) effect appeared to be caused by binding to histones and decreasing DNA-histone interactions. Poly(ADP-ribose) also had high affinity for DNA ligase. These observations, together with the findings of absolute dependence of poly(ADP-ribose) synthetase activity on DNA strand ends and extensive automodification of the synthetase in DNA-damaged cells, suggested a possible mechanism of poly(ADP-ribose) action in DNA repair, in which auto-modified poly(ADP-ribose) synthetase serves as a link between DNA damage and activation of DNA ligase.
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PMID:Inhibition of DNA ligase activity by histones and its reversal by poly(ADP-ribose). 665 29

Phosphorylation of DNA ligase I has been analyzed during Xenopus laevis early development. The enzyme, which is involved in DNA replication and DNA repair events, is accumulated during oogenesis to reach a maximum in the stage VI oocyte, and remains at a constant level during maturation. When maturation of the oocyte is induced (in vivo or in vitro), this leads to a post-translational modification of the protein. In stage VI oocytes, a DNA ligase I of apparent molecular mass 180 kDa is detected immunologically whereas a 190-kDa form is found in unfertilized eggs and persists until the tadpole stage. This modification is due to phosphorylation performed by a protein kinase that is turned on 3-4 h after induction of the maturation. Activation of the kinase requires protein synthesis, and appearance of phosphorylated DNA ligase coincides with activation of histone H1 kinase activity. Induction of DNA ligase I modification and maturation are induced in the absence of protein synthesis following injection of maturation promoting factor into oocytes. Immunoprecipitated oocyte DNA ligase I is phosphorylated and its molecular mass modified by purified cyclin B/p34cdc2 in vitro. DNA ligase I phosphorylation is not induced in oocyte extract where only mitogen-activated-protein kinase is induced. Phosphorylation of DNA ligase I induced by cdc2 kinase occurs at the time new DNA replication and recombination activities appear in eggs.
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PMID:Cyclin B/p34cdc2 triggers phosphorylation of DNA ligase I during Xenopus laevis oocyte maturation. 760 20

The preference of the linker histones to bind to superhelical DNA in comparison with linear or relaxed molecules suggests that these proteins might, in turn, change the twist and/or writhe of DNA molecules upon binding. In order to explore such a possibility, we looked for changes in the linking number of plasmid pBR322 caused by H1 binding, using assays that involve nicking and resealing of DNA strands. Two types of enzymes were used, eukaryotic topoisomerase I and prokaryotic DNA ligase. The results revealed that H1 binding causes unwinding of the DNA, with the unwinding angle being approximately 10 degrees . The globular domain of histone H1 is also capable of unwinding DNA, but to a lesser degree.
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PMID:H1 binding unwinds DNA. Evidence from topological assays. 895 84

We previously reported that HMGB1, which originally binds to chromatin in a manner competitive with linker histone H1 to modulate chromatin structure, enhances both intra-molecular and inter-molecular ligations. In this paper, we found that histone H1 differentially enhances ligation reaction of DNA double-strand breaks (DSB). Histone H1 stimulated exclusively inter-molecular ligation reaction of DSB with DNA ligase IIIbeta and IV, whereas HMGB1 enhanced mainly intra-molecular ligation reaction. Electron microscopy of direct DNA-protein interaction without chemical cross-linking visualized that HMGB1 bends and loops linear DNA to form compact DNA structure and that histone H1 is capable of assembling DNA in tandem arrangement with occasional branches. These results suggest that differences in the enhancement of DNA ligation reaction are due to those in alteration of DNA configuration induced by these two linker proteins. HMGB1 and histone H1 may function in non-homologous end-joining of DSB repair and V(D)J recombination in different manners.
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PMID:Nucleosome linker proteins HMGB1 and histone H1 differentially enhance DNA ligation reactions. 1189 Jul 3