- SMC5/6: Shaping, protecting and preparing the genome for safe reproduction
- Award date
- 1 October 2015
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
SMC5/6 is one of the three structural maintenance of chromosomes (SMC) protein complexes and is involved in numerous processes involving DNA damage repair and genomic integrity maintenance. Although such DNA damage control mechanisms, together with highly dynamic changes in chromatin composition and function, are essential for gametogenesis, knowledge on SMC5/6 function in mammalian systems is limited.
The aim of this thesis is to gain understanding in the mechanisms that shape, protect and prepare the genome for one of the most complex and challenging, yet essential, processes of species survival: reproduction. To gain insight in how genomic integrity and stability is maintained during the diverse phases of rodent and human spermatogenesis, we have investigated the possible roles of SMC5/6 herein.
Chapter 2 focusses on possible roles of SMC6 during rodent spermatogonial differentiation and meiosis. Chapter 3 aims to translate recent findings in rodent studies to human, thereby shedding light on the specific genome integrity maintenance mechanism that exist in human germ cells. In an attempt to find a common denominator and thereby create clarity in the field of SMC5/6 research, chapter 4 provides a clear overview of the versatile functions of SMC5/6 during meiosis, from yeast to man. Chapter 5 further focusses on the function and biochemical regulation of SMC5/6 in DNA replication and repair using a cell line model and CRISPR-Cas9 mediated gene targeting. Finally, Chapter 6 aims to discuss the relevance of the obtained results presented in the current thesis and the implications and opportunities for future research.
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