scholarly journals Structural Basis of DNA Ligase IV-Artemis Interaction in Nonhomologous End-Joining

Cell Reports ◽  
2012 ◽  
Vol 2 (6) ◽  
pp. 1505-1512 ◽  
Author(s):  
Pablo De Ioannes ◽  
Shruti Malu ◽  
Patricia Cortes ◽  
Aneel K. Aggarwal
Keyword(s):  
Nonhomologous End Joining ◽  
Structural Basis ◽  
Dna Ligase ◽  
End Joining ◽  
Dna Ligase Iv ◽  
Ligase Iv

scholarly journals Yeast DNA ligase IV mutations reveal a nonhomologous end joining function of BRCT1 distinct from XRCC4/Lif1 binding

DNA Repair ◽  
2014 ◽  
Vol 24 ◽  
pp. 37-45 ◽  
Author(s):  
Kishore K. Chiruvella ◽  
Brian M. Renard ◽  
Shanda R. Birkeland ◽  
Sham Sunder ◽  
Zhuobin Liang ◽  
...  
Keyword(s):  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
End Joining ◽  
Dna Ligase Iv ◽  
Ligase Iv

scholarly journals Mutations of the Yku80 C Terminus and Xrs2 FHA Domain Specifically Block Yeast Nonhomologous End Joining

2005 ◽  
Vol 25 (24) ◽  
pp. 10782-10790 ◽  
Author(s):  
Phillip L. Palmbos ◽  
James M. Daley ◽  
Thomas E. Wilson
Keyword(s):  
Mutational Analysis ◽  
Strand Break ◽  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
End Joining ◽  
Fha Domain ◽  
Dna Ligase Iv ◽  
C Terminus ◽  
Ligase Iv ◽  
Two Hybrid

ABSTRACT The nonhomologous end-joining (NHEJ) pathway of DNA double-strand break repair requires three protein complexes in Saccharomyces cerevisiae: MRX (Mre11-Rad50-Xrs2), Ku (Ku70-Ku80), and DNA ligase IV (Dnl4-Lif1-Nej1). Much is known about the interactions that mediate the formation of each complex, but little is known about how they act together during repair. A comprehensive yeast two-hybrid screen of the NHEJ factors of S. cerevisiae revealed all known interactions within the MRX, Ku, and DNA ligase IV complexes, as well as three additional, weaker interactions between Yku80-Dnl4, Xrs2-Lif1, and Mre11-Yku80. Individual and combined deletions of the Yku80 C terminus and the Xrs2 forkhead-associated (FHA) domain were designed based on the latter two-hybrid results. These deletions synergistically blocked NHEJ but not the telomere and recombination functions of Ku and MRX, confirming that these protein regions are functionally important specifically for NHEJ. Further mutational analysis of Yku80 identified a putative C-terminal amphipathic α-helix that is both required for its NHEJ function and strikingly similar to a DNA-dependent protein kinase interaction motif in human Ku80. These results identify a novel role in yeast NHEJ for the poorly characterized Ku80 C-terminal and Xrs2 FHA domains, and they suggest that redundant binding of DNA ligase IV facilitates completion of this DNA repair event.

scholarly journals XLF Interacts with the XRCC4-DNA Ligase IV Complex to Promote DNA Nonhomologous End-Joining

Cell ◽  
2006 ◽  
Vol 124 (2) ◽  
pp. 301-313 ◽  
Author(s):  
Peter Ahnesorg ◽  
Philippa Smith ◽  
Stephen P. Jackson
Keyword(s):  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
End Joining ◽  
Dna Ligase Iv ◽  
Ligase Iv

scholarly journals Organization and dynamics of the nonhomologous end-joining machinery during DNA double-strand break repair

2015 ◽  
Vol 112 (20) ◽  
pp. E2575-E2584 ◽  
Author(s):  
Dylan A. Reid ◽  
Sarah Keegan ◽  
Alejandra Leo-Macias ◽  
Go Watanabe ◽  
Natasha T. Strande ◽  
...  
Keyword(s):  
Single Molecule ◽  
Strand Break ◽  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
End Joining ◽  
Dna Ligase Iv ◽  
Ligase Iv ◽  
End To End

Nonhomologous end-joining (NHEJ) is a major repair pathway for DNA double-strand breaks (DSBs), involving synapsis and ligation of the broken strands. We describe the use of in vivo and in vitro single-molecule methods to define the organization and interaction of NHEJ repair proteins at DSB ends. Super-resolution fluorescence microscopy allowed the precise visualization of XRCC4, XLF, and DNA ligase IV filaments adjacent to DSBs, which bridge the broken chromosome and direct rejoining. We show, by single-molecule FRET analysis of the Ku/XRCC4/XLF/DNA ligase IV NHEJ ligation complex, that end-to-end synapsis involves a dynamic positioning of the two ends relative to one another. Our observations form the basis of a new model for NHEJ that describes the mechanism whereby filament-forming proteins bridge DNA DSBs in vivo. In this scheme, the filaments at either end of the DSB interact dynamically to achieve optimal configuration and end-to-end positioning and ligation.

scholarly journals DNA Ligase IV Guides End-Processing Choice during Nonhomologous End Joining

Cell Reports ◽  
2017 ◽  
Vol 20 (12) ◽  
pp. 2810-2819 ◽  
Author(s):  
Michael P. Conlin ◽  
Dylan A. Reid ◽  
George W. Small ◽  
Howard H. Chang ◽  
Go Watanabe ◽  
...  
Keyword(s):  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
End Joining ◽  
Dna Ligase Iv ◽  
Ligase Iv

scholarly journals Impact of DNA ligase IV on nonhomologous end joining pathways during class switch recombination in human cells

2005 ◽  
Vol 201 (2) ◽  
pp. 189-194 ◽  
Author(s):  
Qiang Pan-Hammarström ◽  
Anne-Marie Jones ◽  
Aleksi Lähdesmäki ◽  
Wei Zhou ◽  
Richard A. Gatti ◽  
...  
Keyword(s):  
Cytidine Deaminase ◽  
Class Switch Recombination ◽  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
End Joining ◽  
Dna Ligase Iv ◽  
Class Switch ◽  
Recombinational Process ◽  
Ligase Iv ◽  
Number Of Patients

Class switch recombination (CSR) is a region-specific, transcriptionally regulated, nonhomologous recombinational process that is initiated by activation-induced cytidine deaminase (AID). The initial lesions in the switch (S) regions are subsequently processed and resolved, leading to recombination of the two targeted S regions. The mechanisms by which repair and ligation of the broken DNA ends occurs is still elusive. Recently, a small number of patients lacking DNA ligase IV, a critical component of the nonhomologous end joining (NHEJ) machinery, have been identified. We show that these patients display a considerably increased donor/acceptor homology at Sμ–Sα junctions compared with healthy controls. In contrast, Sμ–Sγ junctions show an increased frequency of insertions but no increase in junctional homology. These altered patterns of junctional resolution may be related to differences in the homology between the Sμ and the downstream isotype S regions, and could reflect different modes of switch junction resolution when NHEJ is impaired. These findings link DNA ligase IV, and thus NHEJ, to CSR.

scholarly journals Structural and Functional Interaction between the Human DNA Repair Proteins DNA Ligase IV and XRCC4

2009 ◽  
Vol 29 (11) ◽  
pp. 3163-3172 ◽  
Author(s):  
Peï-Yu Wu ◽  
Philippe Frit ◽  
SriLakshmi Meesala ◽  
Stéphanie Dauvillier ◽  
Mauro Modesti ◽  
...  
Keyword(s):  
Human Fibroblasts ◽  
Dominant Negative ◽  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
Brct Domain ◽  
End Joining ◽  
Tail Region ◽  
Dna Ligase Iv ◽  
Binding Interface ◽  
Ligase Iv

ABSTRACT Nonhomologous end-joining represents the major pathway used by human cells to repair DNA double-strand breaks. It relies on the XRCC4/DNA ligase IV complex to reseal DNA strands. Here we report the high-resolution crystal structure of human XRCC4 bound to the carboxy-terminal tandem BRCT repeat of DNA ligase IV. The structure differs from the homologous Saccharomyces cerevisiae complex and reveals an extensive DNA ligase IV binding interface formed by a helix-loop-helix structure within the inter-BRCT linker region, as well as significant interactions involving the second BRCT domain, which induces a kink in the tail region of XRCC4. We further demonstrate that interaction with the second BRCT domain of DNA ligase IV is necessary for stable binding to XRCC4 in cells, as well as to achieve efficient dominant-negative effects resulting in radiosensitization after ectopic overexpression of DNA ligase IV fragments in human fibroblasts. Together our findings provide unanticipated insight for understanding the physical and functional architecture of the nonhomologous end-joining ligation complex.

scholarly journals DNA ligase IV mutations confer shorter lifespan and increased sensitivity to nutrient stress in Drosophila melanogaster

2021 ◽  
Author(s):  
Rashmi Joshi ◽  
Surya Jyoti Banerjee ◽  
Jennifer Curtiss ◽  
Amanda K. Ashley
Keyword(s):  
Drosophila Melanogaster ◽  
Strand Break ◽  
Nonhomologous End Joining ◽  
Dna Ligase ◽  
End Joining ◽  
Dna Ligase Iv ◽  
Dna Double Strand Break ◽  
Ligase Iv ◽  
Increased Sensitivity

AbstractThe nonhomologous end-joining pathway is a primary DNA double-strand break repair pathway in eukaryotes. DNA ligase IV (Lig4) catalyzes the final step of DNA end ligation in this pathway. Partial loss of Lig4 in mammals causes Lig4 syndrome, while complete loss is embryonically lethal. DNA ligase 4 (DNAlig4) null Drosophila melanogaster is viable, but sensitive to ionizing radiation during early development. We proposed to explore if DNAlig4 loss induced other long-term sensitivities and defects in D. melanogaster. We demonstrated that DNAlig4 mutant strains had decreased lifespan and lower resistance to nutrient deprivation, indicating Lig4 is required for maintaining health and longevity in D. melanogaster.

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