p21 provides stage specific DNA damage control to preimplantation embryos

Adiga, Satish Kumar; Toyoshima, Megumi; Shiraishi, Kazunori; Shimura, Tsutomu; Takeda, Jun; Taga, Masataka; Nagai, H.; Kumar, Pratap; Niwa, Ohtsura

doi:10.1038/sj.onc.1210444

Cited by 68 publications

(68 citation statements)

References 32 publications

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“…Bcas2 mNull zygotes cleaved into two-cell embryos without obvious developmental delays but arrested at the zygotic stage with increased DNA damage upon HU treatment, supporting the notion that the checkpoint is activated in a dosage dependent manner in mouse zygotes (Adiga et al, 2007;Grinfeld and Jacquet, 1987). Thus, it is possible that damaged DNA does not activate the checkpoint in Bcas2 mNull zygotes, which cleave into two-cell stage embryos.…”

Section: Discussionmentioning

confidence: 50%

Maternal BCAS2 protects genomic integrity in mouse early embryonic development

Wang

Xiang

et al. 2015

Development

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Mammalian early embryos maintain accurate genome integrity for proper development within a programmed timeline despite constant assaults on their DNA by replication, DNA demethylation and genetic defects transmitted from germ cells. However, how genome integrity is safeguarded during mammalian early embryonic development remains unclear. BCAS2 (breast carcinoma amplified sequence 2), a core component of the PRP19 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 damage in mouse zygotes. Maternal depletion of BCAS2 compromises the DNA damage response in early embryos, leading to developmental arrest at the two-to four-cell stage accompanied by the accumulation of damaged DNA and micronuclei. Furthermore, BCAS2 mutants that are unable to bind RPA1 fail in DNA repair during the zygotic stage. In addition, phosphorylated RPA2 cannot localise to the DNA damage sites in mouse zygotes with disrupted maternal BCAS2. These data suggest that BCAS2 might function through the RPA complex during DNA repair in zygotes. Together, our results reveal that maternal BCAS2 maintains the genome integrity of early embryos and is essential for female mouse fertility.

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Section: Discussionmentioning

confidence: 50%

Maternal BCAS2 protects genomic integrity in mouse early embryonic development

Wang

Xiang

et al. 2015

Development

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“…Additionally, the expression of p21 following DNA damage has been shown to be both p53 dependent and p53 independent (2,10,11,16,34,59) and to be p53 and Klf4 dependent in vitro (19,63). Also, p21 levels have been shown to have a dose-dependent and a cell-cycle dependent effect on the apoptotic or antiapoptotic cell fate (1,32,35,41). Furthermore, results of DNA-damage repair (Fig.…”

Section: Discussionmentioning

confidence: 99%

Krüppel-like factor 4 is a radioprotective factor for the intestine following γ-radiation-induced gut injury in mice

Talmasov

Zhang

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Gathering facts from our earlier data [11] and other studies [12,13], there is apparently evidence to show that fertilization with DNA damaged sperm induces variety of biological response in embryos and even increases the risk of transgenerational genomic instability in both somatic as well as germ cell compartment of first generation offspring [5].…”

Section: Discussionmentioning

confidence: 99%

Nuclear DNA fragmentation negatively affects zona binding competence of Y bearing mouse spermatozoa

Kumar

Upadhya

Uppangala

et al. 2013

J Assist Reprod Genet

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Purpose To investigate the influence of sperm DNA integrity on the zona binding ability of mouse spermatozoa in relation to their sex chromosomal constitution. Method(s) In this prospective experimental study, the sperm DNA fragmentation was induced by exposing testicular area of Swiss Albino mice (Mus musculus ) to different doses of γ-radiation (0, 2.5, 5.0 and 10.0 Gy). Sperm DNA fragmentation was quantified by single cell gel electrophoresis (comet assay). In vitro sperm zona binding assay was performed and the numbers of zona bound X and Y bearing spermatozoa were determined using fluorescence in situ hybridization (FISH). Result(s) The assessment of zona pellucida bound X and Ybearing spermatozoa using fluorescence in situ hybridization has revealed a unique binding pattern. The number of zona bound Y-spermatozoa declined significantly (P <0.01 to 0.0001) with increase in the DNA damage. The skewed binding pattern of X and Y-bearing sperm was strongly correlated with the extent of sperm DNA damage. Conclusion(s) The zona pellucida may have a role in preventing DNA damaged mouse sperm binding especially towards Y-bearing sperm. However, the exact mechanism behind this observation needs to be elucidated further.

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p21 provides stage specific DNA damage control to preimplantation embryos

Cited by 68 publications

References 32 publications

Maternal BCAS2 protects genomic integrity in mouse early embryonic development

Maternal BCAS2 protects genomic integrity in mouse early embryonic development

Krüppel-like factor 4 is a radioprotective factor for the intestine following γ-radiation-induced gut injury in mice

Nuclear DNA fragmentation negatively affects zona binding competence of Y bearing mouse spermatozoa

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