Events Calendar

Molecular Toxicology Journal Club

EOH student Pattra Chun-on will present the article:

"Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy"

Khattar E, Maung KZY, Chew CL, Ghosh A, Mok MMH, Lee P, Zhang J, Chor WHJ, Cildir G, Wang CQ, Mohd-Ismail NK, Chin DWL, Lee SC, Yang H, Shin YJ, Nam DH, Chen L, Kumar AP, Deng LW, Ikawa M, Gunaratne J, Osato M, Tergaonkar V.

Abstract
Increased levels and non-telomeric roles have been reported for shelterin proteins, including RAP1 in cancers. Herein using Rap1 null mice, we provide the genetic evidence that mammalian Rap1 plays a major role in hematopoietic stem cell survival, oncogenesis and response to chemotherapy. Strikingly, this function of RAP1 is independent of its association with the telomere or with its known partner TRF2. We show that RAP1 interacts with many members of the DNA damage response (DDR) pathway. RAP1 depleted cells show reduced interaction between XRCC4/DNA Ligase IV and DNA-PK, and are impaired in DNA Ligase IV recruitment to damaged chromatin for efficient repair. Consistent with its role in DNA damage repair, RAP1 loss decreases double-strand break repair via NHEJ in vivo, and consequently reduces B cell class switch recombination. Finally, we discover that RAP1 levels are predictive of the success of chemotherapy in breast and colon cancer.

PLEASE SUPPORT OUR STUDENT PRESENTERS

Organized by Dr. Nicholas Fitz of the Department of Environmental and Occupational Health, this weekly course is designed to expose EOH students to the newest and most exciting research in a diverse set of topics related to toxicology.  Guests are welcome.

Dial-In Information

Contact Dr. Nicholas Fitz (nffitz@pitt.edu) for Zoom information to attend.

Thursday, August 27 at 11:00 a.m. to 12:00 p.m.

Virtual Event

Molecular Toxicology Journal Club

EOH student Pattra Chun-on will present the article:

"Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy"

Khattar E, Maung KZY, Chew CL, Ghosh A, Mok MMH, Lee P, Zhang J, Chor WHJ, Cildir G, Wang CQ, Mohd-Ismail NK, Chin DWL, Lee SC, Yang H, Shin YJ, Nam DH, Chen L, Kumar AP, Deng LW, Ikawa M, Gunaratne J, Osato M, Tergaonkar V.

Abstract
Increased levels and non-telomeric roles have been reported for shelterin proteins, including RAP1 in cancers. Herein using Rap1 null mice, we provide the genetic evidence that mammalian Rap1 plays a major role in hematopoietic stem cell survival, oncogenesis and response to chemotherapy. Strikingly, this function of RAP1 is independent of its association with the telomere or with its known partner TRF2. We show that RAP1 interacts with many members of the DNA damage response (DDR) pathway. RAP1 depleted cells show reduced interaction between XRCC4/DNA Ligase IV and DNA-PK, and are impaired in DNA Ligase IV recruitment to damaged chromatin for efficient repair. Consistent with its role in DNA damage repair, RAP1 loss decreases double-strand break repair via NHEJ in vivo, and consequently reduces B cell class switch recombination. Finally, we discover that RAP1 levels are predictive of the success of chemotherapy in breast and colon cancer.

PLEASE SUPPORT OUR STUDENT PRESENTERS

Organized by Dr. Nicholas Fitz of the Department of Environmental and Occupational Health, this weekly course is designed to expose EOH students to the newest and most exciting research in a diverse set of topics related to toxicology.  Guests are welcome.

Dial-In Information

Contact Dr. Nicholas Fitz (nffitz@pitt.edu) for Zoom information to attend.

Thursday, August 27 at 11:00 a.m. to 12:00 p.m.

Virtual Event

Event Type

Virtual

Topic

Research