ATRX Promotes DNA Repair Synthesis and Sister Chromatid Exchange during Homologous Recombination
| Autor: | Markus Löbrich, Arthur Mathes, Amira Elbakry, Szilvia Juhász |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
X-linked Nuclear Protein RAD51 Sister chromatid exchange Biology Histones 03 medical and health sciences 0302 clinical medicine Death-associated protein 6 Proliferating Cell Nuclear Antigen Sister chromatids Humans DNA Breaks Double-Stranded Replication Protein C Molecular Biology ATRX Adaptor Proteins Signal Transducing Nuclear Proteins Recombinational DNA Repair Cell Biology Chromatin Proliferating cell nuclear antigen Cell biology 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Rad51 Recombinase Homologous recombination Co-Repressor Proteins Sister Chromatid Exchange HeLa Cells Molecular Chaperones |
| Zdroj: | Molecular cell. 71(1) |
| ISSN: | 1097-4164 |
| Popis: | ATRX is a chromatin remodeler that, together with its chaperone DAXX, deposits the histone variant H3.3 in pericentromeric and telomeric regions. Notably, ATRX is frequently mutated in tumors that maintain telomere length by a specific form of homologous recombination (HR). Surprisingly, in this context, we demonstrate that ATRX-deficient cells exhibit a defect in repairing exogenously induced DNA double-strand breaks (DSBs) by HR. ATRX operates downstream of the Rad51 removal step and interacts with PCNA and RFC-1, which are collectively required for DNA repair synthesis during HR. ATRX depletion abolishes DNA repair synthesis and prevents the formation of sister chromatid exchanges at exogenously induced DSBs. DAXX- and H3.3-depleted cells exhibit identical HR defects as ATRX-depleted cells, and both ATRX and DAXX function to deposit H3.3 during DNA repair synthesis. This suggests that ATRX facilitates the chromatin reconstitution required for extended DNA repair synthesis and sister chromatid exchange during HR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|