FBXW7-mediated CHK2 regulation modulates DNA damage response and cellular stability in Huntington's disease.

ABSTRACT: DNA damage activates the DNA damage response (DDR) machinery. However, aging impairs DDR in neurons, thereby increasing susceptibility to neurodegenerative diseases, such as Huntington's disease (HD). The mutant huntingtin (mHTT) protein interferes with DNA repair, leading to DNA lesions and a feedback loop of cellular stress that accelerates neurodegeneration. Although the individual roles of FBXW7, ATM, and checkpoint kinase (CHK) are well-known in DDR, their combined roles in HD remain unclear. In this study, we investigated the FBXW7-mediated CHK2 pathway in HD, in which mHTT levels increase, whereas wild-type (WT) HTT levels decrease. HD cells containing mHTT or expanded polyQ-HTT were more prone to DNA damage than cells containing wtHTT or normal-length polyQ, demonstrating the incre

SUBMITTER: Kang TE 

PROVIDER: S-EPMC12583571 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature