| PICH is a helicase of the SNF2 family of ATPases and is essential for proper chromosome segregation during mitosis. While PICH was originally proposed to participate in spindle assembly checkpoint signaling (1), that function was subsequently called into question. When phosphorylated at Thr1063 by CDK1, PICH binds the polo-box domain of the mitotic kinase PLK1 and targets it to chromosome arms, where it appears to facilitate proper chromosome arm cohesion. PICH is also a substrate of PLK1. Localized to the cytoplasm during interphase, PICH begins to accumulate at centromeres and kinetochores in prometaphase. As chromosomes begin to separate at the onset of anaphase, PICH associates with ultrafine threads between sister centromeres thought to be composed of entangled DNA, a natural consequence of DNA replication. PICH is proposed to cooperate with BLM, a RecQ-like helicase implicated in the genetic disorder Bloom’s Syndrome, to displace centromeric histones along these threads, thus enabling them to span large distances without breaking. This provides a temporal window for topoisomerase IIα-mediated disentanglement. Defects in PICH or BLM disrupt proper chromatid segregation and result in the formation of micronuclei. |
