The UVSSA protein is part of a genome integrity homeostasis network with links to transcription-coupled DNA repair and ATM signaling.
Proc Natl Acad Sci U S A
; 119(11): e2116254119, 2022 03 15.
Article
em En
| MEDLINE
| ID: mdl-35254895
ABSTRACT
SignificanceTranscription-coupled repair (TCR) involves four core proteins CSA, CSB, USP7, and UVSSA. CSA and CSB are mutated in the severe human neurocutaneous disease Cockayne syndrome. In contrast UVSSA is a mild photosensitive disease in which a mutated protein sequence prevents recruitment of USP7 protease to deubiquitinate and stabilize CSB. We deleted the UVSSA protein using CRISPR-Cas9 in an aneuploid cell line, HEK293, and determined the functional consequences. The knockout cell line was sensitive to transcription-blocking lesions but not sensitive to oxidative agents or PARP inhibitors, unlike CSB. Knockout of UVSSA also activated ATM, like CSB, in transcription-arrested cells. The phenotype of UVSSA, especially its rarity, suggests that many TCR-deficient patients and tumors fail to be recognized clinically.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Transdução de Sinais
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Proteínas de Transporte
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Reparo do DNA
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Proteínas Mutadas de Ataxia Telangiectasia
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Homeostase
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article