5WQD

Crystal structure of TRF2 TRFH in complex with an NBS1 peptide

Summary for 5WQD

• Entry DOI: 10.2210/pdb5wqd/pdb
• Descriptor: Telomeric repeat-binding factor 2, Nibrin (2 entities in total)
• Functional Keywords: telomere, shelterin complex, dna damage response, cell cycle
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : Q15554 O60934
• Total number of polymer chains: 14
• Total formula weight: 179206.25

Authors

Hu, C.,Chen, Y.,Lei, M. (deposition date: 2016-11-26, release date: 2017-03-08, Last modification date: 2023-11-08)

Primary citation

Rai, R.,Hu, C.,Broton, C.,Chen, Y.,Lei, M.,Chang, S.
NBS1 Phosphorylation Status Dictates Repair Choice of Dysfunctional Telomeres
Mol. Cell, 65:801-817.e4, 2017

PubMed Abstract: Telomeres employ TRF2 to protect chromosome ends from activating the DNA damage sensor MRE11-RAD50-NBS1 (MRN), thereby repressing ATM-dependent DNA damage checkpoint responses. How TRF2 prevents MRN activation at dysfunctional telomeres is unclear. Here, we show that the phosphorylation status of NBS1 determines the repair pathway choice of dysfunctional telomeres. The crystal structure of the TRF2-NBS1 complex at 3.0 Å resolution shows that the NBS1 YQLSP motif interacts specifically with the TRF2 domain. Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2, promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres. Classical-NHEJ-mediated repair of telomeres lacking TRF2 requires phosphorylated NBS1 to activate ATM, while interaction of de-phosphorylated NBS1 with TRF2 promotes alternative-NHEJ repair of telomeres lacking POT1-TPP1. Our work advances understanding of how the TRF2 domain orchestrates telomere end protection and reveals how the phosphorylation status of the NBS1 dictates repair pathway choice of dysfunctional telomeres.

PubMed: 28216226
DOI: 10.1016/j.molcel.2017.01.016

Experimental method

X-RAY DIFFRACTION (3 Å)