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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.8
- 수록면
- 799 - 807 (9page)
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Emerging evidence has suggested that cellular crosstalk between RNF168 and poly(ADP-ribose) polymerase 1 (PARP1) contributes to the precise control of the DNA damage response (DDR). However, the direct and reciprocal functional link between them remains unclear. In this report, we identified that RNF168 ubiquitinates PARP1 via direct interaction and accelerates PARP1 degradation in the presence of poly (ADP-ribose) (PAR) chains, metabolites of activated PARP1. Through mass spectrometric analysis, we revealed that RNF168 ubiquitinated multiple lysine residues on PARP1 via K48-linked ubiquitin chain formation. Consistent with this, micro-irradiation-induced PARP1 accumulation at damaged chromatin was significantly increased by knockdown of en-dogenous RNF168. In addition, it was confirmed that abnormal changes of HR and HNEJ due to knockdown of RNF168 were restored by overex-pression of WT RNF168 but not by reintroduction of mutants lacking E3 ligase activity or PAR binding ability. The comet assay also revealed that both PAR-binding and ubiquitin-conjugation activities are indispensable for the RNF168-mediated DNA repair process. Taken together, our results suggest that RNF168 acts as a counterpart of PARP1 in DDR and regulates the HR/NHEJ repair processes through the ubiquitination of PARP1.
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참고문헌 (20)
참고문헌 신청
Andrabi, S.A. / 2011 / Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death / Nat. Med. 17:692~699
Ciccia, A. / 2010 / The DNA damage response: making it safe to play with knives / Mol. Cell. 40:179~204
David, K.K. / 2009 / Parthanatos, a messenger of death / Front Biosci (Landmark Ed). 14:1116~1128
Gatti, M. / 2015 / RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage / Cell Rep 10:226~238
Gibson, B.A. / 2012 / New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs / Nat. Rev. Mol. Cell Biol. 13:411~424
Ciccia, A. / 2010 / The DNA damage response: making it safe to play with knives / Mol. Cell. 40:179~204
David, K.K. / 2009 / Parthanatos, a messenger of death / Front Biosci (Landmark Ed). 14:1116~1128
Gatti, M. / 2015 / RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage / Cell Rep 10:226~238
Gibson, B.A. / 2012 / New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs / Nat. Rev. Mol. Cell Biol. 13:411~424
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