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Mol Biol Cell. 2017 Jan 1;28(1):192-200. doi: 10.1091/mbc.E16-08-0573. Epub 2016 Nov 9.

Chromatin association of XRCC5/6 in the absence of DNA damage depends on the XPE gene product DDB2.

Author information

1
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois, Chicago, IL 60607.
2
Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, MA 02115.
3
Department of Oral Biology, College of Dentistry, University of Illinois, Chicago, IL 60612.
4
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois, Chicago, IL 60607 pradip@uic.edu.
5
Jesse Brown VA Medical Center, Chicago, IL 60612.

Abstract

Damaged DNA-binding protein 2 (DDB2), a nuclear protein, participates in both nucleotide excision repair and mRNA transcription. The transcriptional regulatory function of DDB2 is significant in colon cancer, as it regulates metastasis. To characterize the mechanism by which DDB2 participates in transcription, we investigated the protein partners in colon cancer cells. Here we show that DDB2 abundantly associates with XRCC5/6, not involving CUL4 and DNA-PKcs. A DNA-damaging agent that induces DNA double-stranded breaks (DSBs) does not affect the interaction between DDB2 and XRCC5. In addition, DSB-induced nuclear enrichment or chromatin association of XRCC5 does not involve DDB2, suggesting that the DDB2/XRCC5/6 complex represents a distinct pool of XRCC5/6 that is not directly involved in DNA break repair (NHEJ). In the absence of DNA damage, on the other hand, chromatin association of XRCC5 requires DDB2. We show that DDB2 recruits XRCC5 onto the promoter of SEMA3A, a DDB2-stimulated gene. Moreover, depletion of XRCC5 inhibits SEMA3A expression without affecting expression of VEGFA, a repression target of DDB2. Together our results show that DDB2 is critical for chromatin association of XRCC5/6 in the absence of DNA damage and provide evidence that XRCC5/6 are functional partners of DDB2 in its transcriptional stimulatory activity.

PMID:
28035050
PMCID:
PMC5221623
DOI:
10.1091/mbc.E16-08-0573
[Indexed for MEDLINE]
Free PMC Article

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