Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair

Abstract

In human cells, efficient global genomic repair of DNA damage induced by ultraviolet radiation requires the p53 tumor suppressor, but the mechanism has been unclear. The p48 gene is required for expression of an ultraviolet radiation-damaged DNA binding activity and is disrupted by mutations in the subset of xeroderma pigmentosum group E cells that lack this activity. Here, we show that p48 mRNA levels strongly depend on basal p53 expression and increase further after DNA damage in a p53-dependent manner. Furthermore, like p53 ؊͞؊ cells, xeroderma pigmentosum group E cells are deficient in global genomic repair. These results identify p48 as the link between p53 and the nucleotide excision repair apparatus.

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

“…Although the type of DNA lesion preferentially targeted by each mechanism is known, 183 notably, there is evidence for direct interaction between components of the different repair systems as well as between DNA repair and the p53 pathway. [186][187][188][189][190][191][192][193][194] Although loss of apoptotic/senescent function in theory should be expected to cause therapy resistance, the opposite may be the case in DNA repair. Drugs like alkylating agents generate 8-oxoguanine and single-strand breaks subject to repair by BER, whereas platinum-containing compounds generate interstrand crosslinks and double-strand breaks.…”

E2F regulates DDB2: consequences for DNA repair in Rb-deficient cells

“…Human DDB2 expression has been shown to be regulated by p53 at both basal level and after DNA damage (Hwang et al, 1999) when p53 binds to a consensus site in the 5 0 untranslated region of DDB2 gene and stimulates DDB2 transcription (Tan and Chu, 2002).…”

“…Mutations in the DDB2 gene are associated with the xeroderma pigmentosum group E (XPE) complementation group, which is characterized by deficiency in GGR (Hwang et al, 1999). DDB2 is a small protein that associates with DDB1 to form the UV-damaged DNA binding (UVDDB) complex.…”

Maintenance of genomic integrity by p53: complementary roles for activated and non-activated p53

“…As sequence-speci®c transactivation of p53 target genes is regarded as the major function of p53 after its activation, upregulation of genes involved in DNA repair might be envisioned as a ®rst step to initiate repair of DNA damage. However, with the exception of the gadd45 gene (Kastan et al, 1992), and the p48 xeroderma pigmentosum gene (Hwang et al, 1999), which have been linked to DNA repair, no such direct e ect of p53 is known. One thus has to conclude that DNA repair during a p53-induced growth arrest occurs in a p53-independent manner, or alternatively, that p53 participates in DNA repair by other activities.…”