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NBS1 Recruits RAD18 via a RAD6-like Domain and Regulates Pol η-Dependent Translesion DNA Synthesis
- Source :
- Molecular Cell, 43, 5, pp. 788-97, Molecular Cell, 43, 788-97
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Translesion DNA synthesis, a process orchestrated by monoubiquitinated PCNA, is critical for DNA damage tolerance. While the ubiquitin-conjugating enzyme RAD6 and ubiquitin ligase RAD18 are known to monoubiquitinate PCNA, how they are regulated by DNA damage is not fully understood. We show that NBS1 (mutated in Nijmegen breakage syndrome) binds to RAD18 after UV irradiation and mediates the recruitment of RAD18 to sites of DNA damage. Disruption of NBS1 abolished RAD18-dependent PCNA ubiquitination and Polη focus formation, leading to elevated UV sensitivity and mutation. Unexpectedly, the RAD18-interacting domain of NBS1, which was mapped to its C terminus, shares structural and functional similarity with the RAD18-interacting domain of RAD6. These domains of NBS1 and RAD6 allow the two proteins to interact with RAD18 homodimers simultaneously and are crucial for Polη-dependent UV tolerance. Thus, in addition to chromosomal break repair, NBS1 plays a key role in translesion DNA synthesis.<br />放射線の修復蛋白NBS1放によるRAD18を介した損傷乗り越えDNA合成の開始. 京都大学プレスリリース. 2011-09-02.
- Subjects :
- DNA Replication
DNA Repair
Ultraviolet Rays
DNA repair
DNA polymerase
DNA damage
Cell Cycle Proteins
DNA-Directed DNA Polymerase
Auto-immunity, transplantation and immunotherapy [N4i 4]
DNA polymerase delta
Cell Line
Mice
Proliferating Cell Nuclear Antigen
Animals
Humans
Molecular Biology
Cells, Cultured
Mice, Knockout
chemistry.chemical_classification
DNA ligase
biology
DNA synthesis
Ubiquitination
Nuclear Proteins
DNA
Cell Biology
Molecular biology
Cell biology
Ubiquitin ligase
DNA-Binding Proteins
chemistry
Mutation
Ubiquitin-Conjugating Enzymes
biology.protein
DNA mismatch repair
DNA Damage
Subjects
Details
- ISSN :
- 10972765
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Molecular Cell
- Accession number :
- edsair.doi.dedup.....51420b6bed4a65da053e17a3c7f9fb2e