Mouse Rad9b is essential for embryonic development and promotes resistance to DNA damage.
RAD9 participates in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, apoptosis, embryogenesis, and regulation of transcription. A paralogue of RAD9 (named RAD9B) has been identified. To define the function of mouse Rad9b (Mrad9b), embryonic stem (ES) cells with a targeted gene deletion were constructed and used to generate Mrad9b mutant mice. Mrad9b(-/-) embryos are resorbed after E7.5 while some of the heterozygotes die between E12.5 and a few days after birth. Mrad9b is expressed in embryonic brain and Mrad9b(+/-) embryos exhibit abnormal neural tube closure. Mrad9b(-/-) mouse embryonic fibroblasts are not viable. Mrad9b(-/-) ES cells are more sensitive to gamma rays and mitomycin C than Mrad9b(+/+) controls, but show normal gamma-ray-induced G2/M checkpoint control. There is no evidence of spontaneous genomic instability in Mrad9b(-/-) cells. Our findings thus indicate that Mrad9b is essential for embryonic development and mediates resistance to certain DNA damaging agents.
Leloup
Corinne
C
Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Hopkins
Kevin M
KM
Wang
Xiangyuan
X
Zhu
Aiping
A
Wolgemuth
Debra J
DJ
Lieberman
Howard B
HB
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D004249:DNA Damage / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase / Q000235:genetics / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D012854:Sister Chromatid Exchange
D018797:Cell Cycle Proteins; C069930:rad9 protein