学術雑誌論文

学術雑誌論文

Nature Communications. 2019, 10(1), p. 5349

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

Nature Research

英語

2019-12-13

https://doi.org/10.1038/s41467-019-13082-9

Khattar, E., Maung, K.Z.Y., Chew, C.L. et al. Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy. Nat Commun 10, 5349 (2019). https://doi.org/10.1038/s41467-019-13082-9

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.

© 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.

78555

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

Nature Research

英語

2019-12-13

Nature Communications

10

1

5349

https://doi.org/10.1038/s41467-019-13082-9

31836706

https://hdl.handle.net/11094/78555