High fidelity DNA replication and repair: new structures and mechanisms using cryogenic electron microscopy

Borsellini, A. (2022)

Doctoral Thesis

Introduction contains a general overview of the research topics discussed in this thesis.
Chapter 1 addresses a fundamental question in DNA mismatch repair, which is how ATP binding and hydrolysis drive the conformational changes in MutS that
are needed for the mismatch repair cascade.
Chapter 2 focuses on the final stages of the DNA mismatch repair pathway, which are the resection and subsequent resynthesis of the mismatch containing strand.
Chapter 3 presents an example of how DNA polymerases can be targeted for the development of novel antibiotics against Mycobacterium tuberculosis (Mtb).
Chapter 4 describes a new instrument named the Puffalot, developed for the preparation of cryo-EM grids, which aims to improve the reliability of cryo-EM sample preparation.
Discussion provides a summary of the scientific findings described in this thesis in light of the published literature as well as an overview of the future directions and perspectives.

• DNA replication
• DNA mismatch repair
• Cryo EM
• Antibiotic resistance

• All authors: Borsellini, A.
• Supervisor: Neefjes, J.J.C.
• Co-supervisor: Lamers, M.H.
• Committee: Tijsterman, M.; Sixma, T.; Attikum, H. van; Leiro, R.F.; Noordermeer, S.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2022-10-19