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 Biomedical Graduate Studies

CAMB 650 DNA Damage Checkpoints and DNA Repair

CAMB 650 – DNA Damage Checkpoints and DNA repair

Monday, 3-6pm

BRB 301

Course Directors

Eric J. Brown, PhD

Craig Bassing, PhD

Asst Prof of Cancer Bio

Asst Prof of Path & Lab Med and Cancer Bio

U. Penn. School of Medicine

U. Penn. School of Medicine

510 BRB II/III, mail code 6160

816E Abramson Research Center

(215) 746-2805, FAX (215) 573-2486

(267) 426-0311, Fax (267) 426-5165

brownej@mail.med.upenn.edu

bassing@mail.med.upenn.edu

Brad Johnson, MD, PhD

Asst Prof of Pathology & Lab. Medicine

U. Penn. School of Medicine

405A Stellar-Chance/6100

215-573-5037

johnsonb@mail.med.upenn.edu

Teaching assistants

Marina Kozak

Julie Norseen

Johnson Lab

Lieberman Lab

Stellar Chance

Room 406

The Wistar Institute, room 201

3601 Spruce Street

(215) 573-6529

(215) 898-9523

kozak2@mail.med.upenn.edu

norseen@mail.med.upenn.edu

Description:

DNA damage checkpoint and repair genes are important suppressors of cancer and aging. These processes function as part of a complex interconnected network of DNA recognition and processing, checkpoint signaling cascades and DNA repair. Because these processes preserve genome integrity, how they cooperate with one another is directly related to their ability to suppress cancer and aging. To study this emerging research area, students in CAMB 650 will critically evaluate key research findings published in the last five years. In addition to providing an advanced understanding of DNA damage checkpoints, DNA repair and the connections of these processes with cancer and aging, this course is designed to allow students to gain experience in critiquing scientific literature both independently and through group discussion.

Prerequisites:  Previous completion of CAMB 530 or BMB 585 is required to provide the necessary background for this course. To maximize discussion, class size will be limited to no more than 12 students.

Class Format:

Each week, a topic in DNA damage responses will be covered.  One to two review/reference papers and 2-3 primary research papers will be assigned for reading and analysis per week.  A 15 minute introduction to the topic will be given by the instructor at the time of assignment.  Papers will be accompanied by a questionnaire (10-12 multi-part questions) addressing the research area, data, methods and the author’s and student’s interpretations of the data.  In the following week, students will return their answers to the questionnaires for grading and engage in a round table discussion of the papers. In discussion, students will be given the opportunity to argue their points of view on the papers. This course will be taught in one session per week (3 hours) to foster exploration of how the papers relate to each other and the general research area.

Topics (one per week):

M 1/8

Introduction to DNA damage checkpoints and DNA repair. History and present state of the field (Brown, Bassing and Johnson)

M 1/22

Types of DNA damage, e.g. metabolic, exogenous, telomere erosion as DNA damage, programmed breaks (Bassing)

M 1/29

DNA repair: homologous recombination (Johnson)

M 2/5

Checkpoints, cell cycle arrest and apoptosis (Brown)

M 2/12

Checkpoints and genome integrity (Brown)

M 2/19

Chromatin modification in DNA repair (Bassing)

M 2/26

Midterm: Connections between checkpoints and DNA repair (Brown)

M 3/5

DNA damage and cancer: when checkpoints fail (Brown)

M 3/12

DNA damage and cancer: when repair fails (Bassing)

M 3/19

Connections between checkpoints/repair and telomere maintenance (Johnson)

M 3/26

Genome integrity and aging (Johnson)

M 4/2

Final:  Future research areas explored, individual student meetings

M 4/9

Final:  Discussion of future research areas

Grading:

Take home questionnaire assignments and participation in class discussions will make up 45% and 25% of each student’s final grade, respectively.  A midterm exam (10% of final grade) will ask students to prepare a questionnaire to thoroughly critique two assigned research papers.  In the final two weeks of the course, each student will study and propose a future research topic in field of DNA damage responses, cancer and aging.  Students will be expected to pose a question and propose how the question will be experimentally answered.  In the final week of the course, each student will turn in a one page description of their proposal and will present their proposal to fellow students for discussion and critique.  The proposal and presentation will comprise 15% each student’s final grade; 5% of the final grade will be determined by participation in the critiquing the presentations.