Suv420 enrichment at the centromere limits Aurora B localization and function

Abstract

Centromere structure and function are defined by the epigenetic modification of histones at centromeric and pericentromeric chromatin. The constitutive heterochromatin found at pericentromeric regions is highly enriched for H3K9me3 and H4K20me3. While mis-expression of the methyltransferase enzymes, Suv39 and Suv420, that regulate these marks are common in disease, the consequences of such changes are not well understood. Our data show that increased centromere localization of Suv39 and Suv420 suppress centromere transcription and compromise localization of the mitotic kinase Aurora B: decreasing microtubule dynamics and compromising chromosome alignment and segregation. We find that inhibition of Suv420 methyltransferase activity partially restores Aurora B localization to centromeres and that restoration of the Aurora B-containing CPC to the centromere is sufficient to suppress mitotic errors that result when Suv420/H4K20me3 is enriched at centromeres. Consistent with a role for Suv39 and Suv420 in negatively regulating Aurora B, high expression of these enzymes corresponds with increased sensitivity to Aurora kinase inhibition in cancer cells suggesting that increased H3K9 and H4K20 methylation may be an underappreciated source of chromosome missegregation in cancer.

Suppression of chromosome instability limits acquired drug resistance

“…Cultured cells or single cell suspensions derived from tumors were grown on coverslips, fixed, and stained for Aurora B (BD Biosciences, #611082), ACA (Antibodies Inc, #15-234), tubulin (Santa Cruz, #5286), CENPA S7p (Cell Signaling, #2187), and/or CENPA (Enzo Life Sciences, ADI-KAM-CC006-E) as previously described [19, 20]. To assess kinetochore microtubule stability cells were incubated in ice cold RPMI for 5 minutes (PC9 and A549) or 10 minutes…”

Diversity in Plastic Surgery and the 2023 US Supreme Court Decision

“…Following the Supreme Court decision to prohibit colleges from admitting students solely based on their race, companies are starting to opt out of diversity commitments. Fortune 100 chief executive officers have been warned not to consider race as a factor during the hiring process 13,14 …”

“…Experts believe the Supreme Court decision ruling against affirmative action in higher education could dismantle diversity, equity, and inclusion programs in corporate America 13,14 . Corporations could be held liable for “wokeism” in their diversity, equity, and inclusion programs and policies.…”

“…Corporations could be held liable for “wokeism” in their diversity, equity, and inclusion programs and policies. Will Hild, executive director of Consumer's Research, believes that companies that prioritize race in staffing decisions are violating the Civil Rights Act 14 . Companies engaging in hiring promotion schemes that are explicitly racially based could be exposed to litigation.…”

“…If it comes out in emails or communications that, they may not have said it on the job application, but they were discriminating quietly within the company, they're not going to have any legal defense at this point that their goals were noble and so it's OK. It's just flat-out illegal now.” Gene Hamilton, general counsel for America First Legal concurs, “If I was advising major corporations and law schools and medical schools and everything else, I would tell them to immediately get out of the business of racial preferences and out of the business of racial quotas.” 14 …”