Chromosome missegregation during anaphase triggers p53 cell cycle arrest through histone H3.3 Ser31 phosphorylation

摘要: Maloriented chromosomes can evade the spindle assembly checkpoint and generate aneuploidy, a common feature of tumorigenesis. But chromosome missegregation in non-transformed cells triggers p53-dependent fail-safe mechanism that blocks proliferation normal inadvertently become aneuploid. How this is triggered not known. Here we identify conserved feedback monitors missegregating during anaphase through differential phosphorylation histone H3.3 at Ser31. We do by inducing transient diploid cells. During anaphase, Ser31 phosphorylated along arms lagging or misaligned chromosomes. Within minutes, (Ser31P) spreads to all chromatids both daughter cells, which persists into G1. Masking Ser31P antibody microinjection prevents nuclear p53 accumulation aneuploid daughters. Previous work demonstrated prolonged prometaphase DNA damage abnormal mitosis activate p53. show activation response occur without damage. Our study provides insight how aneuploidy caused normally monitored suppressed.