Rosin Leah, Mellone Barbara G
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA; Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA.
Dev Cell. 2016 Apr 18;37(2):136-47. doi: 10.1016/j.devcel.2016.03.021.
Centromeres mediate the conserved process of chromosome segregation, yet centromeric DNA and the centromeric histone, CENP-A, are rapidly evolving. The rapid evolution of Drosophila CENP-A loop 1 (L1) is thought to modulate the DNA-binding preferences of CENP-A to counteract centromere drive, the preferential transmission of chromosomes with expanded centromeric satellites. Consistent with this model, CENP-A from Drosophila bipectinata (bip) cannot localize to Drosophila melanogaster (mel) centromeres. We show that this result is due to the inability of the mel CENP-A chaperone, CAL1, to deposit bip CENP-A into chromatin. Co-expression of bip CENP-A and bip CAL1 in mel cells restores centromeric localization, and similar findings apply to other Drosophila species. We identify two co-evolving regions, CENP-A L1 and the CAL1 N terminus, as critical for lineage-specific CENP-A incorporation. Collectively, our data show that the rapid evolution of L1 modulates CAL1-mediated CENP-A assembly, suggesting an alternative mechanism for the suppression of centromere drive.
着丝粒介导染色体分离这一保守过程,然而着丝粒DNA和着丝粒组蛋白CENP-A却在快速进化。果蝇CENP-A环1(L1)的快速进化被认为可调节CENP-A的DNA结合偏好,以对抗着丝粒驱动,即着丝粒卫星序列扩展的染色体的优先传递。与该模型一致,双栉果蝇(bip)的CENP-A无法定位于黑腹果蝇(mel)的着丝粒。我们发现,这一结果是由于mel CENP-A伴侣蛋白CAL1无法将bip CENP-A沉积到染色质中。在mel细胞中共表达bip CENP-A和bip CAL1可恢复着丝粒定位,类似的结果也适用于其他果蝇物种。我们确定了两个共同进化的区域,即CENP-A L1和CAL1的N端,它们对于特定谱系的CENP-A整合至关重要。总体而言,我们的数据表明L1的快速进化调节了CAL1介导的CENP-A组装,这提示了一种抑制着丝粒驱动的替代机制。