TP53BP1 regulates chromosome alignment and spindle bipolarity in mouse oocytes

Abstract

Meiotic oocytes lack classic centrosomes; therefore, bipolar spindle assembly depends on the clustering of acentriolar microtubule‐organizing centers (MTOCs) into two poles. The bipolar spindle is an essential cellular component that ensures accurate chromosome segregation during anaphase. If the spindle does not form properly, it can result in aneuploidy or cell death. However, the molecular mechanism by which the bipolar spindle is established is not yet fully understood. Tumor suppressor p53‐binding protein 1 (TP53BP1) is known to mediate the DNA damage response. Several recent studies have indicated that TP53BP1 has noncanonical roles in processes, such as spindle formation; however, the role of TP53BP1 in oocyte meiosis is currently unclear. Our results show that TP53BP1 knockdown affects spindle bipolarity and chromatin alignment by altering MTOC stability during oocyte maturation. TP53BP1 was localized in the cytoplasm and displayed an irregular cloud pattern around the spindle/chromosome region. TP53BP1 was also required for the correct localization of MTOCs into the two spindle poles during pro‐meiosis I. TP53BP1 deletion altered the MTOC‐localized Aurora Kinase A. TP53BP1 knockdown caused the microtubules to detach from the kinetochores and increased the rate of aneuploidy. Taken together, our data show that TP53BP1 plays crucial roles in chromosome stability and spindle bipolarity during meiotic maturation.

ESRP1-Mediated Alternative Splicing During Oocyte Development is Required for Mouse Fertility

“…Tumor suppressor p53 binding protein 1 (Trp53bp1) plays a role in maintaining the bipolar spindle during mitosis (Lambrus et al 2016). Recent studies have revealed that Trp53bp1 knockdown affects spindle bipolarity and chromatin alignment by altering MTOC stability during oocyte maturation (Jin et al 2019). In our present study, we also found abnormal splicing of Rac1, which has previously been shown to contribute to spindle positioning and oocyte cortical polarity during mouse oocyte meiosis (Halet and Carroll 2007).…”

Investigation of the mechanisms leading to human sperm DNA damage based on transcriptome analysis by RNA-seq techniques

“…PMS1, MLH1, and MSH2 are likely to form a ternary complex during the initiation of eukaryotic DNA mismatch repair (Prolla et al, 1994). Numerous researches have revealed that tumor suppressor p53-binding protein 1 (TP53BP1) is a central transducer of DNA-damage signals to p53, may work together in the p53-mediated transcriptional activation and DNA damage-repair signaling pathways (Ma et al, 2006), plays an essential role in the cellular response to DNA damage, chromosome stability and spindle bipolarity during meiotic maturation (Jin et al, 2019).…”

The DNA Damage Response in Fully Grown Mammalian Oocytes

“…Another DSB repair protein, the tumor suppressor p53-binding protein 1 (TP53BP1), also seems to affect spindle formation. RNAi for TP53BP1 impairs oocyte maturation by destabilizing microtubule organizing centers (MTOC) which causes the formation of nonbipolar spindles and chromosome misalignment [ 61 ].…”