NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol eta-dependent translesion DNA synthesis

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Title:	NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol eta-dependent translesion DNA synthesis
Author(s):	Yanagihara, H.; Kobayashi, J.; Tateishi, S.; Kato, A.; Matsuura, S.; Tauchi, H.; Yamada, K.; Takezawa, J.; Sugasawa, K.; Masutani, C.; Hanaoka, F.; Weemaes, C.M.R. ; Mori, T.; Zou, L.; Komatsu, K.
Publication year:	2011
Source:	Molecular Cell, vol. 43, iss. 5, (2011), pp. 788-797
ISSN:	1097-2765
DOI:	https://doi.org/10.1016/j.molcel.2011.07.026
Publication type:	Article / Letter to editor
Please use this identifier to cite or link to this item : https://hdl.handle.net/2066/96131
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Subject:	N4i 4: Auto-immunity, transplantation and immunotherapy
Organization:	Paediatrics
Journal title:	Molecular Cell
Volume:	vol. 43
Issue:	iss. 5
Page start:	p. 788
Page end:	p. 797
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 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.