GSBS Student Publications

Title

The FANCJ/MutLalpha interaction is required for correction of the cross-link response in FA-J cells

Publication Date

2007-06-22

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cancer Biology

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

FANCJ also called BACH1/BRIP1 was first linked to hereditary breast cancer through its direct interaction with BRCA1. FANCJ was also recently identified as a Fanconi anemia (FA) gene product, establishing FANCJ as an essential tumor suppressor. Similar to other FA cells, FANCJ-null (FA-J) cells accumulate 4N DNA content in response to DNA interstrand crosslinks (ICLs). This accumulation is corrected by reintroduction of wild-type FANCJ. Here, we show that FANCJ interacts with the mismatch repair complex MutLalpha, composed of PMS2 and MLH1. Specifically, FANCJ directly interacts with MLH1 independent of BRCA1, through its helicase domain. Genetic studies reveal that FANCJ helicase activity and MLH1 binding, but not BRCA1 binding, are essential to correct the FA-J cells' ICL-induced 4N DNA accumulation and sensitivity to ICLs. These results suggest that the FANCJ/MutLalpha interaction, but not FANCJ/BRCA1 interaction, is essential for establishment of a normal ICL-induced response. The functional role of the FANCJ/MutLalpha complex demonstrates a novel link between FA and MMR, and predicts a broader role for FANCJ in DNA damage signaling independent of BRCA1.

DOI of Published Version

10.1038/sj.emboj.7601754

Source

EMBO J. 2007 Jul 11;26(13):3238-49. Epub 2007 Jun 21. Link to article on publisher's site

Journal/Book/Conference Title

The EMBO journal

Related Resources

Link to article in PubMed

PubMed ID

17581638

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