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Structural and functional involvement of p53 in BER in vitro and in vivo.

Abstract：

:p53 is involved in several DNA repair pathways. Some of these require the specific transactivation of p53-dependent genes and others involve direct interactions between the p53 protein and DNA repair associated proteins. Previously, we have shown that p53 acts directly in Base Excision Repair (BER) when assayed under in vitro conditions. Our present data indicate that this involvement is independent of the transcriptional activity of the p53 molecule. We found that under both in vitro and in vivo conditions, a p53 transactivation-deficient molecule, p53-22-23 was more efficient in BER activity than was wild type p53. However, mutations in the core domain or C-terminal alterations strongly reduced p53-mediated BER activity. These results are consistent with the hypothesis that the involvement of p53 in BER activity, a housekeeping DNA repair pathway, is a prompt and immediate one that does not involve the activation of p53 transactivation-dependent mechanisms, but rather concerns with the p53 protein itself. In an endogenous DNA damage status p53 is active in BER pathways as a protein and not as a transcription factor.

journal_name

Oncogene

journal_title

Oncogene

authors

Offer H,Milyavsky M,Erez N,Matas D,Zurer I,Harris CC,Rotter V

doi

10.1038/sj.onc.1204120

subject

Has Abstract

pub_date

2001-02-01 00:00:00

pages

581-9

issue

5

eissn

0950-9232

issn

1476-5594

journal_volume

20

pub_type

杂志文章

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