NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol eta-dependent translesion DNA synthesis
Publication year
2011Source
Molecular Cell, 43, 5, (2011), pp. 788-97ISSN
Publication type
Article / Letter to editor

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Organization
Paediatrics - OUD tm 2017
Journal title
Molecular Cell
Volume
vol. 43
Issue
iss. 5
Page start
p. 788
Page end
p. 97
Subject
N4i 4: Auto-immunity, transplantation and immunotherapyAbstract
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 Poleta 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 Poleta-dependent UV tolerance. Thus, in addition to chromosomal break repair, NBS1 plays a key role in translesion DNA synthesis.
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- Academic publications [227425]
- Faculty of Medical Sciences [86157]
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