Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan
Authors: Karthik B Jeganathan
Meelad M Dawlaty
Lauren Seaburg
Santiago Reyes
Jan M van Deursen
Liviu Malureanu
Darren J Baker
Andre Terzic
Atta Behfar
Tobias Wijshake
Bart van de Sluis
Ruben Crespo-Diaz
Janine H van Ree
Virginia Shapiro
Journal: Nature Cell Biology (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: BubR1 gene; mitotic regulator; chromosomes; aneuploidy; premature ageing
Affiliations: Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905, USA.

Abstract:  The BubR1 gene encodes for a mitotic regulator that ensures accurate segregation of chromosomes through its role in the mitotic checkpoint and the establishment of proper microtubule-kinetochore attachments. Germline mutations that reduce BubR1 abundance cause aneuploidy, shorten lifespan and induce premature ageing phenotypes and cancer in both humans and mice. A reduced BubR1 expression level is also a feature of chronological ageing, but whether this age-related decline has biological consequences is unknown. Using a transgenic approach in mice, we show that sustained high-level expression of BubR1 preserves genomic integrity and reduces tumorigenesis, even in the presence of genetic alterations that strongly promote aneuplodization and cancer, such as oncogenic Ras. We find that BubR1 overabundance exerts its protective effect by correcting mitotic checkpoint impairment and microtubule-kinetochore attachment defects. Furthermore, sustained high-level expression of BubR1 extends lifespan and delays age-related deterioration and aneuploidy in several tissues. Collectively, these data uncover a generalized function for BubR1 in counteracting defects that cause whole-chromosome instability and suggest that modulating BubR1 provides a unique opportunity to extend healthy lifespan. 

Retracted: No

PubPeer comments:
 Figure 2, middle rat panels. Some datapoint clusters (sets of 5-6 dots) appear to look very similar to each other in their constellation. I highlighted these with colored ellipses. Note that some sets of 6 or so dots appear to look similar if they are shown mirrored vertically. Is this expected? ![file] , 
 Hi, Elisabeth. Thank you for raising the questions. First of all, we would like to apologize for the figure you saw as it is not high-resolution hence these patterns are blurred and might seem quite similar due to the low definition. Here I present you more high-quality figure in which you can see the patterns of the dots more clearly. Also we provide here the original data. As for the vertically mirrored dots you were wondering about, the software prism automatically shows the dots this way to avoid the points with the same EC50 values overlapped. ![file] ![file] , 
 According to my personal experience, because of the small sample size (n=5 in each group) and the small scale of Y axis, it is indeed possible that the general structure of the dot plot is similar, but in fact the two data are different. I havenu2019t read the original text, and I donu2019t know if the supplemental materials of the original text has original data. I suggest the author should provide the original data to avoid disputes. ,