Biphasic recruitment of TRF2 to DNA damage sites promotes non-sister chromatid homologous recombination repair
Abstract
TRF2 binds to telomeric repeats and is critical for telomere integrity. Evidence suggests that it also localizes to non-telomeric DNA damage sites. However, this recruitment appears to be precarious and functionally controversial. We find that TRF2 recruitment to damage sites occurs by a two-step mechanism: the initial rapid recruitment (phase I) and stable and prolonged association with damage sites (phase II). Phase I is poly(ADP-ribose) polymerase (PARP)-dependent and requires the N-terminal basic domain. The phase II recruitment requires the C-terminal MYB/SANT domain and the iDDR region in the hinge domain, which is mediated by the MRE11 complex and is stimulated by hTERT. PARP-dependent recruitment of intrinsically disordered proteins contributes to transient displacement of TRF2 that separates two phases. TRF2 binds to the I-PpoI-induced DNA double-strand break sites, which is enhanced by the presence of complex damage and is dependent on PARP and the MRE11 complex. TRF2 depletion affects non-sister chromatid homologous recombination (HR) repair, but not HR between sister chromatids or non-homologous endjoining pathways. Our results demonstrate a unique recruitment mechanism and function of TRF2 at non-telomeric DNA damage sites.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2018
- Source ID
- 10.1242/jcs.219311
Entities
People
- Gladys Mae Saquilabon Cruz
- Kyoko Yokomori
- Michael W. Berns
- Sally Loyal Trinh
- Xiangduo Kong
- Xu-dong Zhu
Organizations
- Air Force Office of Scientific Research
- Canadian Institutes of Health Research
- David and Lucile Packard Foundation
- McMaster University
- National Science Foundation
- University of California
- University of California, Irvine