Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:5.99.1.2 (
topoisomerase
)
9,166
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We have identified a region of the beta-globin gene that is attached constitutively to histone-depleted murine erythroleukemia cell nuclei. This region spans 800 bp and is located at -300 to -1100 bp upstream from the site of transcriptional initiation. Attachment is not altered by transcriptional activation of the beta-globin gene during induction to terminal differentiation, and the same region of the beta-globin gene is attached to histone-depleted myeloma cell nuclei (
NS-1
). The attached region contains an A/T-rich section, in addition to a sequence closely related to the Drosophila
topoisomerase
II consensus cleavage sequence. No comparable site of attachment of the alpha 1-globin gene was detected when a region spanning 1.5 kb 5' to 0.5 kb 3' of the region of transcription was studied.
...
PMID:Constitutive attachment of murine erythroleukemia cell histone-depleted DNA loops to nuclear scaffolding is found in the beta-major but not the alpha 1-globin gene. 322 84
The
NS-1
gene of the parvovirus minute virus of mice encodes a multifunctional protein essential for viral DNA replication and gene expression. In addition to possessing DNA helicase and ATPase activities,
NS-1
forms a covalent linkage with the 5' ends of viral DNA and is a strong candidate for the site-specific
nicking-closing enzyme
postulated to be involved in the resolution of concatemers and terminal hairpin structures that arise during parvoviral DNA replication. Since the covalent linkage between
NS-1
and the 5' terminus of MVM DNA resists alkali and mild acid treatment, a tyrosine phosphodiester is likely to be involved. To map domains responsible for this activity, mutations converting tyrosine to phenylalanine were introduced into the
NS-1
gene using oligonucleotide-directed mutagenesis and their effect on the DNA replication and transcriptional activation functions of
NS-1
was examined in transient in vivo transfection assays. Replacement of Tyr-188, Tyr-197, Tyr-210, Tyr-310, Tyr-422, or Tyr-550 with phenylalanine greatly reduced the ability of
NS-1
to complement the replication of the target genome ins 20B in COS-7 cells. However, a Ser-545 to Thr-545 substitution in the Phe-550 mutant restored DNA replication activity. Replacement of 5 other tyrosines in
NS-1
with phenylalanine either enhanced (Phe-6), had a moderate inhibitory effect (Phe-209) or had no effect (Phe-47, Phe 227 and Phe-543) on its DNA replication activity. Two of the 11 phenylalanine substitution mutations, Phe-188 and Phe-197, also greatly reduced the ability of
NS-1
to transactivate the p38 promoter and displayed a dominant negative phenotype with respect to transactivation. Since the remaining tyrosines in MVM
NS-1
, Tyr-152, Tyr-252, Tyr-374, and Tyr-595, are not conserved among the
NS-1
proteins encoded by porcine and feline parvoviruses, they are presumed to be nonessential for the normal functioning of
NS-1
. The results point to a role for either Tyr-188, Tyr-197, Tyr-210, Tyr-310, or Tyr-422 in forming a covalent linkage with viral DNA and further suggest a regulatory role for several tyrosines in other DNA replication and transcriptional activation functions of
NS-1
.
...
PMID:Mutational analysis of conserved tyrosines in the NS-1 protein of the parvovirus minute virus of mice. 850 71
