DNA-translocation-independent role of INO80 remodeler in DNA damage repairs.
J Biol Chem
; 299(10): 105245, 2023 10.
Article
en En
| MEDLINE
| ID: mdl-37696438
ABSTRACT
Chromatin remodelers utilize ATP hydrolysis to reposition histone octamers on DNA, facilitating transcription by promoting histone displacements. Although their actions on chromatin with damaged DNA are assumed to be similar, the precise mechanisms by which they modulate damaged nucleosomes and their specific roles in DNA damage response (DDR) remain unclear. INO80-C, a versatile chromatin remodeler, plays a crucial role in the efficient repair of various types of damage. In this study, we have demonstrated that both abasic sites and UV-irradiation damage abolish the DNA translocation activity of INO80-C. Additionally, we have identified compromised ATP hydrolysis within the Ino80 catalytic subunit as the primary cause of the inhibition of DNA translocation, while its binding to damaged nucleosomes remains unaffected. Moreover, we have uncovered a novel function of INO80-C that operates independently of its DNA translocation activity, namely, its facilitation of apurinic/apyrimidinic (AP) site cleavage by the AP-endonuclease 1 (APE1). Our findings provide valuable insights into the role of the INO80-C chromatin remodeler in DDR, thereby advancing our understanding of chromatin remodeling during DNA damage repairs.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
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Histonas
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Nucleosomas
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Proteínas de Saccharomyces cerevisiae
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Reparación del ADN
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2023
Tipo del documento:
Article