scholarly journals Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining

2015 ◽  
Vol 43 (14) ◽  
pp. 7021-7031 ◽  
Author(s):  
Vandna Kukshal ◽  
In-Kwon Kim ◽  
Gregory L. Hura ◽  
Alan E. Tomkinson ◽  
John A. Tainer ◽  
...  
Keyword(s):  
Dna Ligase ◽  
End Joining ◽  
Human Dna ◽  
Dna Ends ◽  
Dna Ligase Iii

scholarly journals Human DNA Ligase III Recognizes DNA Ends by Dynamic Switching between Two DNA-Bound States

Biochemistry ◽  
2010 ◽  
Vol 49 (29) ◽  
pp. 6165-6176 ◽  
Author(s):  
Elizabeth Cotner-Gohara ◽  
In-Kwon Kim ◽  
Michal Hammel ◽  
John A. Tainer ◽  
Alan E. Tomkinson ◽  
...  
Keyword(s):  
Bound States ◽  
Dna Ligase ◽  
Dynamic Switching ◽  
Human Dna ◽  
Dna Ends ◽  
Dna Ligase Iii

scholarly journals DNA Ligase III as a Candidate Component of Backup Pathways of Nonhomologous End Joining

2005 ◽  
Vol 65 (10) ◽  
pp. 4020-4030 ◽  
Author(s):  
Huichen Wang ◽  
Bustanur Rosidi ◽  
Ronel Perrault ◽  
Minli Wang ◽  
Lihua Zhang ◽  
...  
Keyword(s):  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
End Joining ◽  
Dna Ligase Iii

scholarly journals Two DNA-binding and Nick Recognition Modules in Human DNA Ligase III

2008 ◽  
Vol 283 (16) ◽  
pp. 10764-10772 ◽  
Author(s):  
Elizabeth Cotner-Gohara ◽  
In-Kwon Kim ◽  
Alan E. Tomkinson ◽  
Tom Ellenberger
Keyword(s):  
Dna Binding ◽  
Dna Ligase ◽  
Human Dna ◽  
Dna Ligase Iii

scholarly journals DNA ligase III and DNA ligase IV carry out genetically distinct forms of end joining in human somatic cells

DNA Repair ◽  
2014 ◽  
Vol 21 ◽  
pp. 97-110 ◽  
Author(s):  
Sehyun Oh ◽  
Adam Harvey ◽  
Jacob Zimbric ◽  
Yongbao Wang ◽  
Thanh Nguyen ◽  
...  
Keyword(s):  
Somatic Cells ◽  
Dna Ligase ◽  
End Joining ◽  
Dna Ligase Iv ◽  
Ligase Iv ◽  
Dna Ligase Iii

scholarly journals The Human DNA Ligase III Gene Encodes Nuclear and Mitochondrial Proteins

1999 ◽  
Vol 19 (5) ◽  
pp. 3869-3876 ◽  
Author(s):  
Uma Lakshmipathy ◽  
Colin Campbell
Keyword(s):  
Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Mitochondrial Protein ◽  
Nuclear Accumulation ◽  
Dna Ligase ◽  
Mitochondrial Enzymes ◽  
Antisense Mrna ◽  
Human Dna ◽  
Green Fluorescent ◽  
Dna Ligase Iii

ABSTRACT We provide evidence that the human DNA ligase III gene encodes a mitochondrial form of this enzyme. First, the DNA ligase III cDNA contains an in-frame ATG located upstream from the putative translation initiation start site. The DNA sequence between these two ATG sites encodes an amphipathic helix similar to previously identified mitochondrial targeting peptides. Second, recombinant green fluorescent protein harboring this sequence at its amino terminus was efficiently targeted to the mitochondria of Cos-1 monkey kidney cells. In contrast, native green fluorescent protein distributed to the cytosol. Third, a series of hemagglutinin-DNA ligase III minigene constructs were introduced into Cos-1 cells, and immunocytochemistry was used to determine subcellular localization of the epitope-tagged DNA ligase III protein. These experiments revealed that inactivation of the upstream ATG resulted in nuclear accumulation of the DNA ligase III protein, whereas inactivation of the downstream ATG abolished nuclear localization and led to accumulation within the mitochondrial compartment. Fourth, mitochondrial protein extracts prepared from human cells overexpressing antisense DNA ligase III mRNA possessed substantially less DNA ligase activity than did mitochondrial extracts prepared from control cells. DNA end-joining activity was also substantially reduced in extracts prepared from antisense mRNA-expressing cells. From these results, we conclude that the human DNA ligase III gene encodes both nuclear and mitochondrial enzymes. DNA ligase plays a central role in DNA replication, recombination, and DNA repair. Thus, identification of a mitochondrial form of this enzyme provides a tool with which to dissect mammalian mitochondrial genome dynamics.

scholarly journals DNA Ligase III Promotes Alternative Nonhomologous End-Joining during Chromosomal Translocation Formation

PLoS Genetics ◽  
2011 ◽  
Vol 7 (6) ◽  
pp. e1002080 ◽  
Author(s):  
Deniz Simsek ◽  
Erika Brunet ◽  
Sunnie Yan-Wai Wong ◽  
Sachin Katyal ◽  
Yankun Gao ◽  
...  
Keyword(s):  
Chromosomal Translocation ◽  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
End Joining ◽  
Dna Ligase Iii

scholarly journals XRCC4/XLF Interaction Is Variably Required for DNA Repair and Is Not Required for Ligase IV Stimulation

2015 ◽  
Vol 35 (17) ◽  
pp. 3017-3028 ◽  
Author(s):  
Sunetra Roy ◽  
Abinadabe J. de Melo ◽  
Yao Xu ◽  
Satish K. Tadi ◽  
Aurélie Négrel ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Double Strand Breaks ◽  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
End Joining ◽  
Strand Breaks ◽  
Ligase Iv ◽  
Cell Strains ◽  
Dna Ends

The classic nonhomologous end-joining (c-NHEJ) pathway is largely responsible for repairing double-strand breaks (DSBs) in mammalian cells. XLF stimulates the XRCC4/DNA ligase IV complex by an unknown mechanism. XLF interacts with XRCC4 to form filaments of alternating XRCC4 and XLF dimers that bridge DNA endsin vitro, providing a mechanism by which XLF might stimulate ligation. Here, we characterize two XLF mutants that do not interact with XRCC4 and cannot form filaments or bridge DNAin vitro. One mutant is fully sufficient in stimulating ligation by XRCC4/Lig4in vitro; the other is not. This separation-of-function mutant (which must function as an XLF homodimer) fully complements the c-NHEJ deficits of some XLF-deficient cell strains but not others, suggesting a variable requirement for XRCC4/XLF interaction in living cells. To determine whether the lack of XRCC4/XLF interaction (and potential bridging) can be compensated for by other factors, candidate repair factors were disrupted in XLF- or XRCC4-deficient cells. The loss of either ATM or the newly described XRCC4/XLF-like factor, PAXX, accentuates the requirement for XLF. However, in the case of ATM/XLF loss (but not PAXX/XLF loss), this reflects a greater requirement for XRCC4/XLF interaction.

scholarly journals Mammalian DNA ligase III: molecular cloning, chromosomal localization, and expression in spermatocytes undergoing meiotic recombination.

1995 ◽  
Vol 15 (10) ◽  
pp. 5412-5422 ◽  
Author(s):  
J Chen ◽  
A E Tomkinson ◽  
W Ramos ◽  
Z B Mackey ◽  
S Danehower ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Chromosome 17 ◽  
Dna Ligase ◽  
Cdna Clones ◽  
Dna Ligases ◽  
Cell Extracts ◽  
Human Dna ◽  
Dna Ligase I ◽  
Dna Ligase Iii

Three biochemically distinct DNA ligase activities have been identified in mammalian cell extracts. We have recently purified DNA ligase II and DNA ligase III to near homogeneity from bovine liver and testis tissue, respectively. Amino acid sequencing studies indicated that these enzymes are encoded by the same gene. In the present study, human and murine cDNA clones encoding DNA ligase III were isolated with probes based on the peptide sequences. The human DNA ligase III cDNA encodes a polypeptide of 862 amino acids, whose sequence is more closely related to those of the DNA ligases encoded by poxviruses than to replicative DNA ligases, such as human DNA ligase I. In vitro transcription and translation of the cDNA produced a catalytically active DNA ligase similar in size and substrate specificity to the purified bovine enzyme. The DNA ligase III gene was localized to human chromosome 17, which eliminated this gene as a candidate for the cancer-prone disease Bloom syndrome that is associated with DNA joining abnormalities. DNA ligase III is ubiquitously expressed at low levels, except in the testes, in which the steady-state levels of DNA ligase III mRNA are at least 10-fold higher than those detected in other tissues and cells. Since DNA ligase I mRNA is also present at high levels in the testes, we examined the expression of the DNA ligase genes during spermatogenesis. DNA ligase I mRNA expression correlated with the contribution of proliferating spermatogonia cells to the testes, in agreement with the previously defined role of this enzyme in DNA replication. In contrast, elevated levels of DNA ligase III mRNA were observed in primary spermatocytes undergoing recombination prior to the first meiotic division. Therefore, we suggest that DNA ligase III seals DNA strand breaks that arise during the process of meiotic recombination in germ cells and as a consequence of DNA damage in somatic cells.

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