p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis
Gamal Ahmed Elfar,
Obed Aning,
Tsz Wai Ngai
et al.
Abstract:Mechanisms underlying p53-mediated protection of the replicating genome remain elusive, despite the quintessential role of p53 in maintaining genomic stability. Here, we uncover an unexpected function of p53 in curbing replication stress by limiting PARP1 activity and preventing the unscheduled degradation of deprotected stalled forks. We searched for p53-dependent factors and elucidated RRM2B as a prime factor. Deficiency in p53/RRM2B results in the activation of an NRF2 antioxidant transcriptional program, w… Show more
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