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Vol. 273, Issue 3, 1794-1801, January 16, 1998
From the The gene product of XRCC4 has been
implicated in both V(D)J recombination and the more general process of
double strand break repair (DSBR). To date its role in these processes
is unknown. Here, we describe biochemical characteristics of the murine
XRCC4 protein. XRCC4 expressed in insect cells exists primarily as a disulfide-linked homodimer, although it can also form large multimers. Recombinant XRCC4 is phosphorylated during expression in insect cells.
XRCC4 phosphorylation in Sf9 cells occurs on serine, threonine, and tyrosine residues.
We also investigated whether XRCC4 interacts with the other factor
known to be requisite for both V(D)J recombination and DSBR, the
DNA-dependent protein kinase. We report that XRCC4 is an
efficient in vitro substrate of DNA-PK and another
unidentified serine/threonine protein kinase(s). Both DNA-PK dependent
and independent phosphorylation of XRCC4 in vitro occurs
only on serine and threonine residues within the COOH-terminal 130 amino acids, a region of the molecule that is not absolutely required
for XRCC4's DSBR function. Finally, recombinant XRCC4 facilitates Ku
binding to DNA, promoting assembly of DNA-PK and complexing with DNA-PK bound to DNA. These data are consistent with the hypothesis that XRCC4
functions as an alignment factor in the DNA-PK complex.
The XRCC4 Gene Product Is a Target for and Interacts with the
DNA-dependent Protein Kinase
,,
Harold C. Simmons Arthritis Research Center, the
Department of Internal Medicine and Program in
Immunology, University of Texas Southwestern Medical Center, Dallas,
Texas 75235 and ¶ The Center for Blood Research and Department of
Genetics, Harvard University Medical School,
Boston, Massachusetts 02115
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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