TY - JOUR
T1 - Promotion of Dnl4-Catalyzed DNA end-joining by the Rad50/Mre11/Xrs2 and Hdf1/Hdf2 complexes
AU - Chen, Ling
AU - Trujillo, Kelly
AU - Ramos, William
AU - Sung, Patrick
AU - Tomkinson, Alan E.
N1 - Funding Information:
We thank Lorraine Symington for the plasmid pSM344 and Maria Gaczynska and Pawel Osmulski for expert assistance with the atomic force microscopy. This work was supported by grants from the United States National Institutes of Health (RO1 GM47251 to A.E.T., RO1 ES07061 and RO1 GM57814 to P.S., PO1 CA81020 to A.E.T./P.S.), Human Frontier Science Program (RG0178/2000-M to P.S.), and the San Antonio Cancer Institute (P30 CA54174).
PY - 2001/11/21
Y1 - 2001/11/21
N2 - S. cerevisiae RAD50, MRE11, and XRS2 genes are required for telomere maintenance, cell cycle checkpoint signaling, meiotic recombination, and the efficient repair of DNA double-strand breaks (DSB)s by homologous recombination and nonhomologous end-joining (NHEJ). Here, we demonstrate that the complex formed by Rad50, Mre11, and Xrs2 proteins promotes intermolecular DNA joining by DNA ligase IV (Dnl4) and its associated protein Lif1. Our results show that the Rad50/Mre11/Xrs2 complex juxtaposes linear DNA molecules via their ends to form oligomers and interacts directly with Dnl4/Lif1. We also demonstrate that Rad50/Mre11/Xrs2-mediated intermolecular DNA joining is further stimulated by Hdf1/Hdf2, the yeast homolog of the mammalian Ku70/Ku80 heterodimer. These studies reveal specific functional interplay among the Hdf1/Hdf2, Rad50/Mre11/Xrs2, and Dnl4/Lif1 complexes in NHEJ.
AB - S. cerevisiae RAD50, MRE11, and XRS2 genes are required for telomere maintenance, cell cycle checkpoint signaling, meiotic recombination, and the efficient repair of DNA double-strand breaks (DSB)s by homologous recombination and nonhomologous end-joining (NHEJ). Here, we demonstrate that the complex formed by Rad50, Mre11, and Xrs2 proteins promotes intermolecular DNA joining by DNA ligase IV (Dnl4) and its associated protein Lif1. Our results show that the Rad50/Mre11/Xrs2 complex juxtaposes linear DNA molecules via their ends to form oligomers and interacts directly with Dnl4/Lif1. We also demonstrate that Rad50/Mre11/Xrs2-mediated intermolecular DNA joining is further stimulated by Hdf1/Hdf2, the yeast homolog of the mammalian Ku70/Ku80 heterodimer. These studies reveal specific functional interplay among the Hdf1/Hdf2, Rad50/Mre11/Xrs2, and Dnl4/Lif1 complexes in NHEJ.
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U2 - 10.1016/S1097-2765(01)00388-4
DO - 10.1016/S1097-2765(01)00388-4
M3 - Article
C2 - 11741545
AN - SCOPUS:0035930342
SN - 1097-2765
VL - 8
SP - 1105
EP - 1115
JO - Molecular Cell
JF - Molecular Cell
IS - 5
ER -