Difference between revisions of "20.109(S17):Module 2"
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For this module, you will examine the effect of NHEJ-targeting drugs on cells that are deficient in homologous recombination, a DNA repair pathway that uses sequence homology to correct double-strand breaks. To this end, you will address several research questions: | For this module, you will examine the effect of NHEJ-targeting drugs on cells that are deficient in homologous recombination, a DNA repair pathway that uses sequence homology to correct double-strand breaks. To this end, you will address several research questions: | ||
| − | #Does drug treatment | + | #Does drug treatment effect cell survival following DNA damage? |
| − | #Does drug treatment | + | #Does drug treatment effect transcription of cell cycle checkpoint regulators following DNA damage? |
#What genes are differentially expressed in response to drug treatment following DNA damage? | #What genes are differentially expressed in response to drug treatment following DNA damage? | ||
Revision as of 00:06, 1 February 2017
Contents
Module 2
Lecturers: Leona Samson and Ernest Fraenkel
Instructors: Noreen Lyell, Leslie McClain and Maxine Jonas
TA: Rob Wilson
Lab manager: Hsinhwa Lee
Overview
Non-homologous end joining (NHEJ) is a pathway of DNA repair by which double-strand breaks are ligated together. In specific types of cancer, targeting NHEJ is an effective treatment option as a paradox exists in cancer. Whole genome sequencing has revealed that the cells of many tumor types have mutations in genes necessary for DNA repair. These mutations are responsible for cells becoming cancerous, but are also detrimental because, just like normal cells, cancer cells must divide to survive. Thus, a cancer cell will develop an ‘addiction’ to a DNA repair pathway – specifically, a pathway different from the one with the mutation that caused the cell to generate a tumor. Recent cancer therapies seek to exploit this addiction by targeting the intact pathway used by the tumor cells to repair DNA damage due to intrinsic breaks that occur during replication. In addition, the effectiveness DNA damage induced by chemotherapy treatment may be enhanced by also disrupting the functional repair pathways of tumor cells.
For this module, you will examine the effect of NHEJ-targeting drugs on cells that are deficient in homologous recombination, a DNA repair pathway that uses sequence homology to correct double-strand breaks. To this end, you will address several research questions:
- Does drug treatment effect cell survival following DNA damage?
- Does drug treatment effect transcription of cell cycle checkpoint regulators following DNA damage?
- What genes are differentially expressed in response to drug treatment following DNA damage?
An additional goal of Module 2 is to give you practice synthesizing data from different experiments into a single story. More often that not, researchers reach conclusions using results gathered from more than one experimental approach.
Lab links: day by day
M2D1: Confirm cell lines and practice tissue culture techniques
M2D2: Complete Western blot and induce DNA damage for survival and quantitative PCR assays
M2D3: Assess cell survival and harvest RNA for quantitative PCR assay
M2D4: Examine transcript levels in response to DNA damage
M2D5: Journal club I
M2D6: Practice data analysis methods
M2D7: Analyze RNA-seq data
M2D8: Journal club II
M2D9: Examine quantitative PCR results
Data
See all M2 student data on the Discussion page.
Assignments
Journal club presentation
Research article
References
- A syngeneic variance library for functional annotation of human variation: application to BRCA2. Cancer Research. 68:5023-5030.
- Synthetic lethality: exploiting the addiction of cancer to DNA repair. Blood Journal. 117:6074-6082.
