Dr. Sarem Hailemariam

Seminar Title: Yeast cell cycle checkpoint regulation in response to DNA breaks and short telomeres

Biography

Sarem received her undergraduate degree in Biology from Shaw University in Raleigh, North Carolina. She joined the Division of Biological and Biomedical Sciences at Washington University in St. Louis in 2012 as part of the Molecular Cell Biology program. Sarem has always been interested in mechanisms employed by different organisms to maintain genome integrity. Prior to joining DBBS, Sarem worked on the mammalian DNA replication origin-licensing factor, Cdt1.

Sarem completed her thesis work in the lab of Dr. Peter Burgers, Brennecke Professor of Biological Chemistry in the department of Biochemistry and Molecular Biophysics. The focus of her thesis work is to understand how eukaryotes regulate cell cycle checkpoint in response to double-stranded DNA breaks (DSBs) and short telomeres. Budding yeast Tel1 kinase initiates cell cycle checkpoint in response to double-strand DNA breaks. Tel1 also plays a major role in telomere maintenance. Tel1’s function both in checkpoint signaling and telomere regulation is dependent on the Mre11-Rad50-Xrs2 (MRX) complex. Using a biochemical approach aimed at reconstituting the initial stages of double-strand DNA break response, our work demonstrates that double-stranded DNA and MRX activate Tel1 synergistically. This MRX and DNA-mediated activation of Tel1 at DNA breaks is important to stall the cell cycle and initiate a DNA damage response-signaling cascade. However, hyper-activation of checkpoint and repair proteins at telomeres could lead to telomere fusion and subsequent genome instability. The ends of chromosomes bare resemblance to one half of a DNA double-strand break. Remodeling of telomeric DNA by telomere binding proteins prevents telomeres from inappropriate recognition and repair as intrachromosomal DNA breaks. Using an in vitro kinase assay, we showed how the yeast telomere binding protein, Rif2, suppresses a Tel1-dependent checkpoint response at telomeres.

Sarem defended her thesis entitled “Regulation of the Yeast Cell Cycle Checkpoint Kinase Tel1 at Double-Strand DNA Breaks and at Telomeres” on 08/20/2019. She is currently working at MilliporeSigma in the R&D group. She’ll continue to mentor young students to help cultivate and nourish their excitement about science.