Heterochromatin links to centromeric protection by recruiting shugoshin

Abstract

The centromere of a chromosome is composed mainly of two domains, a kinetochore assembling core centromere and peri-centromeric heterochromatin regions. The crucial role of centromeric heterochromatin is still unknown, because even in simpler unicellular organisms such as the fission yeast Schizosaccharomyces pombe, the heterochromatin protein Swi6 (HP1 homologue) has several functions at centromeres, including silencing gene expression and recombination, enriching cohesin, promoting kinetochore assembly, and, ultimately, preventing erroneous microtubule attachment to the kinetochores. Here we show that the requirement of heterochromatin for mitotic chromosome segregation is largely replaced by forcibly enriching cohesin at centromeres in fission yeast. However, this enrichment of cohesin is not sufficient to replace the meiotic requirement for heterochromatin. We find that the heterochromatin protein Swi6 associates directly with meiosis-specific shugoshin Sgo1, a protector of cohesin at centromeres. A point mutation of Sgo1 (V242E), which abolishes the interaction with Swi6, impairs the centromeric localization and function of Sgo1. The forced centromeric localization of Sgo1 restores proper meiotic chromosome segregation in swi6 cells. We also show that the direct link between HP1 and shugoshin is conserved in human cells. Taken together, our findings suggest that the recruitment of shugoshin is the important primary role for centromeric heterochromatin in ensuring eukaryotic chromosome segregation.

Reduced ability to recover from spindle disruption and loss of kinetochore spindle assembly checkpoint proteins in oocytes from aged mice

“…54 However, it seems that only heterochromatin protein 1 (HP1) and the SAC protein Bub1 affect Shugoshin recruitment to kinetochores. [55][56][57][58] Therefore, one possibility may be that Sgo2 association with bivalents is not so readily impaired by maternal aging in C57Bl6/J as other chromosome-associated proteins. In contrast, the requirements for pAurora C and Mad2 to attach to kinetochores may be reliant on multiple proteins, whose assembly may be more easily perturbed in the process of aging.…”

A novel tumor-derived SGOL1 variant causes abnormal mitosis and unstable chromatid cohesion

“…Actually, the localization of PP2A-B56a on chromosomes was not affected by SGOL1-P1 expression, even in cells with a reduction in RAD21 signals. Similarly, heterochromatin protein HP1a, a SGOL1-interacting protein that is required for localization and functioning of SGOL1 at the centromere does not seem to be a target either, because the binding region of SGOL1 to HP1a is located in the C-terminal area (Yamagishi et al, 2008). As it is more likely that SGOL1-P1 inhibits the interaction between native SGOL1 and as yet unidentified targets, we are currently searching for proteins that interact with SGOL1-P1.…”

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

“…Pericentric heterochromatin is required for the accumulation of high levels of cohesins, which are critical for chromosome segregation during mitosis (Bernard et al 2001;Nonaka et al 2002;Yamagishi et al 2008). When heterochromatin is compromised, such as in dcr1D, loss of cohesin results in defective attachment of centromeres by microtubules for biorientation.…”