Evolution of CRISPR-associated Endonucleases as Inferred from Resurrected Proteins

CIC nanoGUNE Seminars

Speaker

Ylenia Jabalera, Post-doctoral Researcher, Nanobiotechnology

When

2022/10/03
11:00

Place

nanoGUNE seminar room, Tolosa Hiribidea 76, Donostia - San Sebastian

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**Evolution of CRISPR-associated Endonucleases as Inferred from Resurrected Proteins** Ylenia Jabalera Post-doctoral Researcher, Nanobiotechnology, CIC nanoGUNE Clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 protein is an effector that plays a major role in a prokaryotic adaptive immune system, by which invading DNA can be targeted and cut for inactivation. In this mechanism, the Cas9 endonuclease is directed to target sites by a guide RNA (gRNA) where Cas9 can recognize specific sequences (protospacer- adjacent motif; PAMs) in foreign DNA, which then serve as an anchoring point for cleavage of the adjacent RNA-matching DNA region. Since its discovery, the nature and application of CRISPR-Cas9 systems have been extensively studied. However, its origin and evolution are matter of debate. In this work, we trace the evolutionary history of CRISPR-Cas9 from Streptococcus pyogenes from ancient nucleases (anCas) in extinct firmicutes species 2.6 billion years old to the current day Cas9s. The characterization of anCas proteins and their evolutionary trajectory uncovers unique Cas endonucleases with unexpected properties.