Keep the ORCs at bay : how eukaryotic cells ensure one round of DNA replication per cell cycle

During each cell cycle, eukaryotic cells must faithfully replicate their genome, ensuring exactly one full copy is made. Both under-replicating or over-replicating the genome can have deleterious consequences including cell death, genome instability and cancer. Thus, this process is tightly regulated. The major mechanism to ensure that DNA is replicated once per cell cycle entails the temporal separation of two key replication events: helicase loading and helicase activation. Helicase loading occurs during the G1 phase of the cell cycle. In S. cerevisiae cells, Cyclin-Dependent Kinases (CDKs) prevent helicase loading outside of G1 by phosphorylating three of the four helicase-loading proteins: Mcm2-7, Cdc6, and the Origin Recognition Complex (ORC). Phosphorylation of free Mcm2-7 and Cdc6 leads to their removal from the nucleus (Mcm2-7 by nuclear export and Cdc6 by protein degradation). However, phosphorylated ORC remains in the nucleus bound to origins.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2020

Author dc:creator

• Amasino, Audra Leigh.

Advisor dc:contributor.advisor

• Stephen P. Bell.

• Biology.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/128988

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/128988