TY - JOUR
T1 - Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination
AU - Essers, Jeroen
AU - Hendriks, Rudolf W.
AU - Swagemakers, Sigrid M.A.
AU - Troelstra, Christine
AU - De Wit, Jan
AU - Bootsma, Dirk
AU - Hoeijmakers, Jan H.J.
AU - Kanaar, Roland
N1 - Funding Information:
We are grateful to A. Berns, N. Galjart, G. Grosveld, G. van der Horst, H. te Riele, and G. Weeda for the generous gift of reagents. We thank M. Dronkert, D. van Gent, O. Schärer, and C. Wyman for comments on the manuscript and G. Dingjan, J. Hendrikse, and M. Warle for excellent technical support. We thank J.-M. Buerstedde, W.-D. Heyer, A. Pastink, and S. C. West for discussion. This work was supported by grants from the Dutch Cancer Society (EUR 94–858), The Netherlands Organization for Scientific Research (PGN 901–01–097), and the European Commission (F13PCT920007 and F14PCT950010). R. K. and R. W. H. are fellows of the Royal Netherlands Academy of Arts and Sciences.
PY - 1997/4/18
Y1 - 1997/4/18
N2 - Double-strand DNA break (DSB) repair by homologous recombination occurs through the RAD52 pathway in Saccharomyces cerevisiae. Its biological importance is underscored by the conservation of many RAD52 pathway genes, including RAD54, from fungi to humans. We have analyzed the phenotype of mouse RAD54(-/-) (mRAD54(-/-)) cells. Consistent with a DSB repair defect, these cells are sensitive to ionizing radiation, mitomycin C, and methyl methanesulfonate, but not to ultraviolet light. Gene targeting experiments demonstrate that homologous recombination in mRAD54(-/-) cells is reduced compared to wild-type cells. These results imply that, besides DNA end- joining mediated by DNA-dependent protein kinase, homologous recombination contributes to the repair of DSBs in mammalian cells. Furthermore, we show that mRAD54(-/-) mice are viable and exhibit apparently normal V(D)J and immunoglobulin class-switch recombination. Thus, mRAD54 is not required for the recombination processes that generate functional immunoglobulin and T cell receptor genes.
AB - Double-strand DNA break (DSB) repair by homologous recombination occurs through the RAD52 pathway in Saccharomyces cerevisiae. Its biological importance is underscored by the conservation of many RAD52 pathway genes, including RAD54, from fungi to humans. We have analyzed the phenotype of mouse RAD54(-/-) (mRAD54(-/-)) cells. Consistent with a DSB repair defect, these cells are sensitive to ionizing radiation, mitomycin C, and methyl methanesulfonate, but not to ultraviolet light. Gene targeting experiments demonstrate that homologous recombination in mRAD54(-/-) cells is reduced compared to wild-type cells. These results imply that, besides DNA end- joining mediated by DNA-dependent protein kinase, homologous recombination contributes to the repair of DSBs in mammalian cells. Furthermore, we show that mRAD54(-/-) mice are viable and exhibit apparently normal V(D)J and immunoglobulin class-switch recombination. Thus, mRAD54 is not required for the recombination processes that generate functional immunoglobulin and T cell receptor genes.
UR - http://www.scopus.com/inward/record.url?scp=0030948789&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)80199-3
DO - 10.1016/S0092-8674(00)80199-3
M3 - Article
C2 - 9108475
AN - SCOPUS:0030948789
SN - 0092-8674
VL - 89
SP - 195
EP - 204
JO - Cell
JF - Cell
IS - 2
ER -