Chromosome end protection by RAP1-mediated inhibition of DNA-PK

Chromosome end protection by RAP1-mediated inhibition of DNA-PK

During classical non-homologous end joining (cNHEJ), DNA-dependent protein kinase (DNA-PK) encapsulates free DNA ends, forming a recruitment platform for downstream end-joining factors including ligase 4 (LIG4)1. DNA-PK can also bind telomeres and regulate their resection2–4, but does not initiate cNHEJ at this position. How the end-joining process is regulated in this context-specific manner is currently unclear. Here we show that the shelterin…

JCI ATM-dependent DNA damage response constrains cell growth and drives clonal hematopoiesis in telomere biology disorders

Telomere biology disorders (TBDs) are genetic diseases caused by defective telomere maintenance. TBD patients often develop bone marrow failure and have an increased risk of myeloid neoplasms. To better understand the factors underlying hematopoietic outcomes in TBD, we comprehensively evaluated acquired genetic alterations in hematopoietic cells from 166 pediatric and adult TBD patients. Of these patients, 47.6% (28.8% of children, 56.1% of adu…