Genomic instability in Gadd45a-deficient mice.
Gadd45a-null mice generated by gene targeting exhibited several of the phenotypes characteristic of p53-deficient mice, including genomic instability, increased radiation carcinogenesis and a low frequency of exencephaly. Genomic instability was exemplified by aneuploidy, chromosome aberrations, gene amplification and centrosome amplification, and was accompanied by abnormalities in mitosis, cytokinesis and growth control. Unequal segregation of chromosomes due to multiple spindle poles during mitosis occurred in several Gadd45a -/- cell lineages and may contribute to the aneuploidy. Our results indicate that Gadd45a is one component of the p53 pathway that contributes to the maintenance of genomic stability.
Hollander
M C
MC
Gene Response Section, DBS, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
Sheikh
M S
MS
Bulavin
D V
DV
Lundgren
K
K
Augeri-Henmueller
L
L
Shehee
R
R
Molinaro
T A
TA
Kim
K E
KE
Tolosa
E
E
Ashwell
J D
JD
Rosenberg
M P
MP
Zhan
Q
Q
Fernández-Salguero
P M
PM
Morgan
W F
WF
Deng
C X
CX
Fornace
A J
AJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016922:Cellular Senescence; D018385:Centrosome / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D016193:G1 Phase; D005720:Gamma Rays / Q000009:adverse effects; D017353:Gene Deletion; D011905:Genes, ras / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D013952:Thymus Hyperplasia / Q000235:genetics / Q000473:pathology; D000097642:GADD45 Proteins
D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D000097642:GADD45 Proteins