Laboratory and Basic Science Research Commons^™

Med13p Prevents Stress-Independent Mitochondrial Hyperfragmentation And Aberrant Apoptosis Activation In Saccharomyces Cerevisiae By Controlling Cyclin C Nuclear Localization, Svetlana Khakhina

Graduate School of Biomedical Sciences Theses and Dissertations

During aging, and as a result of environmental changes, cells are exposed to elevated levels of reactive oxygen species (ROS). High ROS levels induce lipid oxidation, protein aggregation, mitochondrial hyperfragmentation, DNA damage and programmed cell death (PCD), also called apoptosis. PCD is a highly regulated process and its misregulation has been linked to neurodegenerative diseases and cancer development.

Our hypothesis is that cyclin C plays a role in the initiation of apoptosis. During normal conditions, cyclin C represses the transcription of stress response genes (SRG). In response to stress, cyclin C translocates to the cytoplasm where it facilitates mitochondrial hyperfragmentation …

Modulation Of Bax/Bak Dependent Apoptosis By Sirtuin 3 And Mitochondrial Permeability Transition By Sirtuin 4, Manish Verma

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondria are dynamic organelles that regulate a myriad of cellular functions, including energy production and metabolic regulation. Mitochondria are also a critical regulator of cell death signaling cascades modulating both apoptotic and necrotic cell death. However, what determines which cell death pathway is activated is still unclear. The mitochondrial/intrinsic pathway of apoptosis is dependent on the activation of pro-apoptotic proteins, Bax and Bak, which induce mitochondrial outer membrane permeabilization (MOMP). Once the integrity of outer mitochondrial membrane (OMM) is compromised, pro-apoptotic intermembrane space proteins like cytochrome c, Smac/Diablo, Omi/HtrA2 and AIF are released into the cytoplasm, which activates the post-mitochondrial …

Novel Roles Of Replication Protein A Phosphorylation In Cellular Response To Dna Damage, Moises A. Serrano

Electronic Theses and Dissertations

Human replication protein A (RPA) is an eukaryotic single-stranded DNA binding protein directly involved in a variety of DNA metabolic pathways including replication, recombination, DNA damage checkpoints and signaling, as well as all DNA repair pathways. This project presents 2 novel roles of RPA in the cellular response to DNA damage. The first elucidates the regulation of RPA and p53 interaction by DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) in homologous recombination (HR). HR and nonhomologous end joining (NHEJ) are 2 distinct DNA double-stranded break (DSB) repair pathways. Here, we report that DNA-PK, the …