The role of autophagy in maintenance of genomic integrity
Autophagy is an intracellular degradation pathway that is important for sustaining cellular metabolism. It is a catabolic process whereby cytoplasmic components such as damaged proteins and organelles are delivered to the lysosomes for degradation. Beyond autophagy’s housekeeping functions, recent s...
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| Format: | Theses and Dissertations |
| Language: | English |
| Published: |
2016
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| Online Access: | https://hdl.handle.net/10356/66007 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | Autophagy is an intracellular degradation pathway that is important for sustaining cellular metabolism. It is a catabolic process whereby cytoplasmic components such as damaged proteins and organelles are delivered to the lysosomes for degradation. Beyond autophagy’s housekeeping functions, recent studies have uncovered a myriad of physiological and pathophysiological roles played by autophagy, such as the modulation of host defenses, ageing and tumorigenesis. In particular, my interest lies in autophagy’s role in maintenance of genomic integrity. However, the mechanisms underlying this role remain elusive. Here, autophagy inhibition resulted in reduced protein levels of condensin-II and Kif4a. This negatively affected the amount of condensin-II and Kif4a localized on the chromosomes and in turn, impeded proper chromosome condensation and kinetochore-microtubule attachments during mitosis. As a result, there was increased incidence of lagging chromosomes from aberrant chromosome segregation, thus compromising genomic integrity. These indicated a pathway where autophagy enables proper chromosome segregation through its regulation on the protein levels of condensin-II and Kif4a. |
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