Week 4. Sensing, signaling, and responding to DNA damage (6 th

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Course # BMSC-GA 4457 Genome Integrity ( 4 credits)

NYU SoM Fall 2015

Course director: Jane Skok

Course Meeting time and location: The class will meet for 2 hours, 2 times a week for 13 weeks. Tues and

Thursday 5-7 in the Skirball 3 rd floor seminar room. Dates are listed below.

Course Description

The goal of this course is to provide graduate students with a broad base in fundamental principles of genome integrity while at the same time providing connections between genome integrity, organismal fitness, and human disease. The course will cover the following areas: (1) DNA metabolism including DNA replication, repair, transposition, and recombination, (2) epigenetic mechanisms that regulate genome function and influence development and disease, and (3) genotoxic stress (induced by radiation, oncogenes or other mechanisms) and its potential in cancer therapies.

Course Assessment

Participation

Exams

Grading scheme: Letter grade

25 %

75 %

Assignments: Students will be assigned a review and a primary paper for each topic.

Readings and participation: Students are required to attend class and to complete reading assignments.

Exam: There will be two in class exams, the first covering weeks 1- 6 and the second covering weeks 8-12.

Course Topics

Week 1. DNA Transposition (3 rd and 10 th Sept )

Transposition and retrotransoposition in eukaryotes

Genome defense against transposable elements

Week 2. DNA Replication (17 th and 24 th Sept)

Boeke

Lehmann

D. Smith

E. Nudler

Replication in Eukaryotes

Week 3. DNA damage (29 th Sept and 1 st October)

The interplay between DNA replication and other processes in bacteria

Sources of DNA damage (metabolic, replication, exogenous, telomere erosion)

Base excision repair, nucleotide repair, and mismatch repair

Week 4. Sensing, signaling, and responding to DNA damage (6 th and 8 th October)

DNA damage sensor proteins

Cell cycle checkpoints

E. Rothenberg

Borowiec

Huang

Pagano

Week 5. Double-strand break repair – 1 (13 th and 15 th October)

Homologous Recombination

Meiosis

Week 6. Double-strand break repair – 2 (20 th and 22 nd October)

Klein

Hochwagen

End-Joining pathways – Classical and Alternative

VDJ and Class Switch Recombination

Week 7. (27 th and 29 th October)

Exam

No class

Week 8. Epigenetics (3 rd and 5 th November)

Altered DNA methylation and genomic instability

Chromatin structure in eukaryotes

Week 9. Maintenance of mitochondrial genome (10 th and 12 th November)

Mitochondrial DNA replication and repair

Non-coding RNAs in Genome Integrity

Week 10. Human Disease (17 th and 19 th November)

Imprinting and X inactivation

Genome integrity and senescence

Week 11. Genotoxic Stress and anti-cancer strategies (24 th November and 1 st December)

Oncogene-induced stress

Radiation therapy

Week 12. Genotoxic Stress and anti-cancer strategies (3 rd December and 8 th December)

PARP inhibitors in cancer therapy

Week 13. (Exam 15 th December)

Centrosome structure, chromosome instability and cancer

No class

Exam

Steir

Skok

Tahiliani

Armache

Sfeir

Serganov

Stadtfeld

David

Bar-Sagi

Schneider

S. Smith

Dynlacht

Exams will consist of a mid-term and end of term final take home questions. Each team will be expected to generate a question that they will then grade (A-C).

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