ARF stimulates XPC to trigger nucleotide excision repair by regulating the repressor complex of E2F4.

Abstract:

:The tumour suppressor ARF (alternative reading frame), which is mutated or silenced in various tumours, has a crucial role in tumour surveillance to suppress unwarranted cell growth and proliferation. ARF has also been linked to the DNA-damage-induced response of p53 because of its ability to inhibit murine double minute 2 (MDM2). Here, however, we provide genetic evidence for a role of ARF in nucleotide excision repair (NER) that is independent of p53. Cells lacking ARF are deficient in NER. Expression of ARF restores the repair activity, which coincides with increased expression of the damaged-DNA recognition protein xeroderma pigmentosum, complementation group C (XPC). We provide evidence that, by disrupting the interaction between E2F transcription factor 4 (E2F4) and DRTF polypeptide 1 (DP1), ARF reduces the interaction of the E2F4-p130 repressor complex with the promoter of XPC to ensure high-level expression of XPC. Together, our results point to an important 'care-taker'-type tumour-suppression function for ARF in NER through the increased expression of XPC.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Dominguez-Brauer C,Chen YJ,Brauer PM,Pimkina J,Raychaudhuri P

doi

10.1038/embor.2009.139

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

1036-42

issue

9

eissn

1469-221X

issn

1469-3178

pii

embor2009139

journal_volume

10

pub_type

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