Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells

Ulf Grawunder, Matthias Wilm, Xiantuo Wu, Peter Kulesza, Thomas E. Wilson, Matthias Mann and Michael R. Lieber ()
Additional contact information
Ulf Grawunder: Washington University School of Medicine
Matthias Wilm: Washington University School of Medicine
Xiantuo Wu: Washington University School of Medicine
Peter Kulesza: Washington University School of Medicine
Thomas E. Wilson: Washington University School of Medicine
Matthias Mann: ‡European Molecular Biology Laboratory (EMBL), Protein & Peptide Group
Michael R. Lieber: Washington University School of Medicine

Nature, 1997, vol. 388, issue 6641, 492-495

Abstract: Abstract Mutation of the XRCC4 gene in mammalian cells1,2 prevents the formation of the signal and coding joints in the V(D)J recombination reaction3, which is necessary for production of a functional immunoglobulin gene, and renders the cells highly sensitive to ionizing radiation4. However, XRCC4 shares no sequence homology with other proteins, nor does it have a biochemical activity to indicate what its function might be2. Here we show that DNA ligase IV (ref. 5) co-immunoprecipitates with XRCC4 and that these two proteins specifically interact with one another in a yeast two-hybrid system. Ligation of DNA double-strand breaks in a cell-free system by DNA ligase IV is increased fivefold by purified XRCC4 and seven- to eightfold when XRCC4 is co-expressed with DNA ligase IV. We conclude that the biological consequences of mutating XRCC4 are primarily due to the loss of its stimulatory effect on DNA ligase IV: the function of the XRCC4–DNA ligase IV complex may be to carry out the final steps of V(D)J recombination and joining of DNA ends.

Date: 1997
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/41358 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:388:y:1997:i:6641:d:10.1038_41358

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/41358

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().