Regulation of double-strand break-induced mammalian homologous recombination by UBL1, a RAD51-interacting protein.
Mammalian RAD51 protein plays essential roles in DNA homologous recombination, DNA repair and cell proliferation. RAD51 activities are regulated by its associated proteins. It was previously reported that a ubiquitin-like protein, UBL1, associates with RAD51 in the yeast two-hybrid system. One function of UBL1 is to covalently conjugate with target proteins and thus modify their function. In the present study we found that non-conjugated UBL1 forms a complex with RAD51 and RAD52 proteins in human cells. Overexpression of UBL1 down-regulates DNA double-strand break-induced homologous recombination in CHO cells and reduces cellular resistance to ionizing radiation in HT1080 cells. With or without overexpressed UBL1, most homologous recombination products arise by gene conversion. However, overexpression of UBL1 reduces the fraction of bidirectional gene conversion tracts. Overexpression of a mutant UBL1 that is incapable of being conjugated retains the ability to inhibit homologous recombination. These results suggest a regulatory role for UBL1 in homologous recombination.
Li
W
W
Department of Molecular Genetics (MC669), College of Medicine, University of Illinois at Chicago, 900 South Ashland Avenue, Chicago, IL 60607, USA,
Hesabi
B
B
Babbo
A
A
Pacione
C
C
Liu
J
J
Chen
D J
DJ
Nickoloff
J A
JA
Shen
Z
Z
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D025842:SUMO-1 Protein; D014162:Transfection; D014452:Ubiquitins / Q000235:genetics*
D004268:DNA-Binding Proteins; D025842:SUMO-1 Protein; D014452:Ubiquitins; D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase