... for multiple rounds of DNA replication, likely via endocycles, in trophoblast giant cells. Furthermore, MYC supports the expression of DNA replication and nucleotide biosynthesis genes along with ribosomal RNA. Increased DNA damage and senescence occur in trophoblast giant cells without Myc , accompanied...

... by a ‘grape’ karyotype, owing to the defects in chromosome alignment. Abnormal alternatively spliced genes related to chromosome segregation, the microtubule cytoskeleton, cell cycle kinases and DNA damage were present in the dhx38 mutants. Subsequently, EMPs and HSPCs in dhx38 mutants underwent P53-dependent...

..., through a mechanism involving DNA damage. Our data suggest that the simultaneous absence of a robust mitotic timer and susceptibility of the embryo to cohesion fatigue could contribute to chromosome instability in mammalian embryos. This article has an associated ‘The people behind the papers’ interview...

... that protein phosphatase 4 catalytic subunit (PPP4C) deletion causes severe female subfertility due to accumulation of DNA damage in oocytes and early embryos. PPP4C dephosphorylated PLK1 at the S137 site, negatively regulating its activity in the DSB response in early embryonic cells. Depletion of PPP4C...

...Ryan S. O'Neill; Nasser M. Rusan ABSTRACT Microcephaly is a failure to develop proper brain size and neuron number. Mutations in diverse genes are linked to microcephaly, including several with DNA damage repair (DDR) functions; however, it is not well understood how these DDR gene mutations limit...

...’ cells, to drive stress resilience during Drosophila renal development and homeostasis . Renal tubules lacking Gadd45 exhibit striking morphogenetic defects (with cell death, inflammatory infiltration and reduced ploidy) and accumulate significant DNA damage in post-embryonic life. In parallel...

... accumulates DNA damage, and mitotic errors ensue when cells are forced to proliferate. In conclusion, we find that wound-induced polyploidization enables tissue repair when cell division is not a viable option. Fig. 8. WIP: an adaptive healing strategy. Model illustrates the adaptive role of polyploid...

...Agnes Miermont; Vlatka Antolović; Tchern Lenn; John M. E. Nichols; Lindsey J. Millward; Jonathan R. Chubb; Allon Klein; Barbara Treutlein ABSTRACT Embryonic development involves extensive and often rapid cell proliferation. An unavoidable side effect of cell proliferation is DNA damage...

... in the microcephalic disorder Seckel syndrome, sustains cerebellar growth by maintaining chromosomal integrity during postnatal neurogenesis. Atr deletion in cerebellar granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis and cerebellar hypoplasia in mice. Co...

... that proliferation of cells with DNA damage is induced in the presence of brain tissue and that the retinoblastoma pathway enables overproliferation of cells with DSBs while attending to the demands of tissue growth and repair. Our results implicate both autonomous and non-autonomous mechanisms as key mediators...

... complex involved in pre-mRNA splicing, plays an important role in the DNA damage response through the RPA complex, a key regulator in the maintenance of genome integrity. Currently, the physiological role of BCAS2 in mammals is unknown. We now report that BCAS2 responds to endogenous and exogenous DNA...

... ). The capacity of cells to respond to potentially detrimental DNA damage is of crucial importance for efficient and accurate replication of the genetic material. Most eukaryotic cells employ highly regulated responses to damaged DNA involving ATR and ataxia telangiectasia mutated (ATM), and their effector...

... differentiating neurons, activated the DNA double-strand break (DSB) repair pathway without increasing trimethylation at lysine 20 of histone H4 (H4K20), which has a role in protection against DNA damage. The activation of the DSB repair pathway was essential for the cell division of Rb-TKO differentiating...

... cyclin, cyclin B1;1, excessive levels of which have been associated with altered microtubules and morphology. Cyclin B1;1 also accumulates in certain backgrounds in response to DNA damage, but we find no evidence for aberrant responses to DNA damage in rsw4 . Our characterization of rsw4 leads us...

... molecular cause of this growth arrest is currently unknown. Here, we show that Arabidopsis csn mutants are delayed in G2 phase progression. This cell cycle arrest correlates with the induction of the DNA damage response pathway and is suggestive of the activation of a DNA damage checkpoint. In support...

... known as loki ) gene encodes Checkpoint kinase 2 (Chk2), which functions in DNA-damage signal transduction. We show that mnk grp double-mutant embryos are replication-checkpoint defective but cellularize, gastrulate and activate high levels of zygotic gene expression. We also show that grp mutant...

... and meiotic cell cycles. Furthermore, they imply that URI-1 participates in a pathway(s) that is associated with the suppression of endogenous genotoxic DNA damage and highlight a role for URI-1 in the control of genome integrity. † Authors for correspondence (e-mail: [email protected]...

... induced by RNAi. The frequency of these defects was accentuated by γ-irradiation, implying that they were derived from spontaneous or induced DNA damage. wrn-1 (RNAi) worms showed accelerated larval growth irrespective of γ-irradiation, and pre-meiotic germ cells had an abnormal checkpoint response to DNA...