THESIS DEFENSE — PUBLIC SEMINAR: T-ALL ASSOCIATED NAP1L1-MLLT10 FUSION PROTEIN PROMOTES TELOMERASE-MEDIATED TELOMERE ELONGATION

Start Date & Time: 
Monday, 20 August, 2018 - 14:00
End Date & Time: 
Monday, 20 August, 2018 - 15:00
Venue: 

Amphitheatre, Level 2,  Duke-NUS

Speaker Details: 

WANG JING
IBM PhD PROGRAM (INTAKE 2013)

Synopsis: 

Telomere length elongation is an essential physiological process necessary for the continuous proliferation of human stem cells and >85% of cancer cells. The enzyme telomerase counteracts telomere attrition by adding TTAGGG repeats to the end of telomeres in human cells. This process is restricted to the late S/G2 phase of the cell cycle and is controlled by regulating the recruitment of telomerase to telomeres. Cell cycle-dependent regulation of telomerase recruitment to telomeres is not only critical for maintaining the telomere length equilibrium, but also for its coupling with DNA replication. However, the molecular mechanisms underlying the cell cycle-dependent telomerase recruitment to telomeres are only partially understood. Here we have identified nucleosome assembly protein 1-like1 (NAP1L1) as a novel TERT-associated protein in human cells. NAP1L1 is a member of histone chaperone family that plays essential roles in DNA replication, chromatin assembly, and cell proliferation. Our data indicates that NAP1L1 interacts with TERT and TRF1 through distinct functional domains and promotes telomerase-mediated telomere elongation. NAP1L1 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) cell lines, and recurrent NAP1L1-MLLT10 fusions have been reported in T-ALL patients. Our data indicates that overexpression of NAP1L1-MLLT10 fusion protein promotes telomere maintenance in cancer cells. These results provide new insights into the mechanisms of telomere maintenance as well as potential strategies for therapeutic intervention of T-ALL with NAP1L1-MLLT10 fusion.