title: Mouse Rad9b is essential for embryonic development and promotes resistance to DNA damage.
abstract: 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.
authors.affiliation: Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Corinne
authors.initials: C
authors.lastname: Leloup
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Hopkins
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Wang
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhu
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Wolgemuth
authors.forename: Howard B
authors.initials: HB
authors.lastname: Lieberman
mesh_terms: 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
chemical_list: D018797:Cell Cycle Proteins; C069930:rad9 protein