Getting the broken blastomere out of development

Cells encounter up to 10 6 DNA damages per day, which can be induced by exogenous physical agents, spontaneous chemical reactions , and products of endogenous metabolism. 1 To cope with these threats, the DNA damage response (DDR) system is employed to detect and repair these damages. if massive DNA damages occur within cells which cannot be repaired properly or promptly, the DDR will cause apoptosis to avoid genomic instability. Accumulated DNA damages in somatic cells lead to tumorigenesis, while DNA damages in early embryos result in developmental failure or death. Traditional methods for studying embryo-logic DNA damage are restricted to drug treatments or radiations. These approaches induce general DNA damages to the whole embryo, without the ability to distinguish the effect on individual blastomeres. with the potential to develop into a complete organism, each blas-tomere is affected by and responds to DNA damage independently. Thus, studying the DDR of individual blastomeres will advance our conventional understanding on embryo response against endogenous and exogenous threats. in this issue of Cell Cycle, by employing a laser microbeam, wang et al. induced DNA damage to a specific single pronucleus of fertilized eggs or blastomere of early embryos and detected the DDR of the individual unit as well as the whole zygote/embryo. 2 As an efficient method to study DDR in somatic cells, 3 laser microbeam is a practical approach to generate DNA damage in early embryos. when targeting a single pronucleus within the fertilized egg, wang et al. found that the DNA damage in either male or female pronucleus caused developmental failure to the blastocyst. 2 More interestingly, when the author induced DNA lesion to a single blas-tomere of 2-cell, 4-cell, or 8-cell embryos, the damaged blastomere ceased cleavage and failed to incorporate into the compacted morula, but instead underwent apoptosis at the blastocyst stage. This response was not caused by direct laser toxicity, since the status of γH2AX staining kept " strand " well, and the nuclear membrane of the blastomere stayed intact. 2 in principle, the response of cells against DNA damage includes cell arrest, DNA repair, senescence, and apoptosis. 4 Unlike somatic cells, blastomeres in early embryos do not repair damaged DNA, but proceed directly to apoptosis. 2 DNA repair will result in inevitable errors, since one of the major repair ways non-homologous end joining is error-prone. 5 To ensure genomic integrity, the embryo must sacrifice the broken blastomere, …