Background

DNA interstrand cross-links (ICL) are covalent bonds between the two strands of the double helix. As they inhibit both transcription and replication, ICLs are one of the most deleterious DNA lesions known. HELQ is a recently discovered helicase that is required for ICL repair.

Method

Proteomic studies, Mass Spectrometry, mouse model studies.

Results

Using Mass Spectrometry we identified RAD51 paralogs as molecular partners of HELQ. Paralogs of RAD51 are involved in Homologus Recombination (HR) however their role remains elusive.

Additionally, we show that HelQ deficient mice are oversensitive to DNA damaging agents and prone to develop cancer. Detailed analysis revealed that the mutant mice are particularly susceptible to develop ovarian cancer. Interestingly a number of recent publication show that germline mutations in genes coding paralogs of RAD51 also predispose to ovarian cancer.

Importantly, screening of human ovarian cancer libraries revealed a pronounce loss of HELQ copy number in malignant ovarian tumours.

Conclusion

HELQ is a novel ICL repair factor that works in the HR branch of the pathway. Although further research needs to be carried out, preliminary data suggest that it might be a new ovarian cancer predisposition factor. Current progress on that will be presented.