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. 2003 May 2;113(3):357-67.
doi: 10.1016/s0092-8674(03)00316-7.

The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage

Regina Groisman  1 , Jolanta Polanowska, Isao Kuraoka, Jun-ichi Sawada, Masafumi Saijo, Ronny Drapkin, Alexei F Kisselev, Kiyoji Tanaka, Yoshihiro Nakatani
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V体育官网入口 - The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage

Regina Groisman et al. Cell. .
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Abstract

Nucleotide excision repair (NER) is a major cellular defense against the carcinogenic effects of ultraviolet light from the sun. Mutational inactivation of NER proteins, like DDB and CSA, leads to hereditary diseases such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS). Here, we show that DDB2 and CSA are each integrated into nearly identical complexes via interaction with DDB1. Both complexes contain cullin 4A and Roc1 and display ubiquitin ligase activity. They also contain the COP9 signalosome (CSN), a known regulator of cullin-based ubiquitin ligases. Strikingly, CSN differentially regulates ubiquitin ligase activity of the DDB2 and CSA complexes in response to UV irradiation VSports手机版. Knockdown of CSN with RNA interference leads to defects in NER. These results suggest that the distinct UV response of the DDB2 and CSA complexes is involved in diverse mechanisms of NER. .

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