Naslov
Ribosomal Protein S6 Gene Haploinsufficiency Is Associated with Activation of a p53-Dependent Checkpoint during Gastrulation

Autori
Panić, Linda ; Tamarut, Sanda ; Sticker-Jantscheff, Melanie ; Barkić, Martina ; Solter, Davor ; Uzelac, Miljana ; Grabušić, Kristina ; Volarević, Siniša

Izvornik
Molecular and cellular biology (0270-7306) 26 (2006), 23; 8880-8891

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
ribosomal protein S6 ; cell cycle ; cell growth ; mouse embryonic development ; p53 checkpoint control

Sažetak
Nascent ribosome biogenesis is required during cell growth. To gain insight into the importance of this process during mouse oogenesis and embryonic development, we deleted one allele of the ribosomal protein S6 gene in growing oocytes and generated S6-heterozygous embryos. Oogenesis and embryonic development until embryonic day 5.5 (E5.5) were normal. However, inhibition of entry into M phase of the cell cycle and apoptosis became evident post-E5.5 and led to perigastrulation lethality. Genetic inactivation of p53 bypassed this checkpoint and prolonged development until E12.5, when the embryos died, showing decreased expression of D-type cyclins, diminished fetal liver erythropoiesis, and placental defects. Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA