Tuesday, November | 11:00 a.m. - 12:00 p.m.
Classroom Building 170 

Universal Principles of Nucleosome Recognition

The human genome is organized in a polymeric chromatin structure composed of repeating nucleosome units. Nuclear proteins bindnucleosomes to execute and regulate genome-templated processes. My research focuses on defining universal principles that govern interactions with nucleosomes. I developed a 
nucleosome affinity proteomic screen to comprehensively assess how nuclear proteins recognize nucleosomes. I found that a group of acidic amino acids on the nucleosome disk surface – referred to as the acidic patch – is the primary hot-spot for nucleosome binding, whereas nearly half of the nucleosome disk participates only minimally in protein recognition. Point mutations within this acidic patch are overrepresented in diverse cancers, adding to a growing list of 
histone oncomutations. To define molecular mechanisms of nucleosome acidic patch interactions and the role of acidic patch oncomutations, I developed a second-generation, high-resolution nucleosome affinity proteomic screen. This screen established footprints of nucleosome acidic patch binding at amino acid resolution for hundreds of proteins and demonstrated that oncomutations disrupt binding of proteins controlling vital cellular processes, such as cell division, gene expression or DNA damage repair, suggesting complex pathogenic mechanisms. Among the most acidic patch-dependent proteins identified in my screens was the Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligase, which had not been previously known to bind to chromatin. I will 
discuss nucleosome affinity proteomics screens and mechanistic studies – including cryo-EM structures – of the APC/C and DNA-free histone complexes.

About the Speaker

Aleksandra Skrajna works as an Assistant Professor at UC Santa Cruz in the Department of Chemistry and Biochemistry. She obtained B.S. in Biotechnology and B.S. in Biophysics, and M.S. in Biotechnology from University of Warsaw, Poland, and Ph.D. in Biophysics from Institute of Biochemistry and Biophysics, Polish Academy of Sciences.

Over the years, the research of Aleksandra Skrajna focused on elucidating the histone life cycle. As a graduate student, she described molecular mechanisms of histone mRNA maturation at the 3'-end; as a postdoc, she defined universal principles governing nucleosome recognition; and now she is studying histone homeostasis. Her group uses multidisciplinary approaches including biochemistry, biophysics, structural and cell biology. Dr. Skrajna was awarded with 2019-2022 American Cancer Society Postdoctoral Fellowship and 2023 Postdoctoral Award for Research Excellence from UNC Chapel Hill; and 2025 Forbeck Scholar Award, Forbeck Foundation.