Helb-KO Mouse

HELB, also known as DNA Helicase B, is a conserved helicase in higher eukaryotes. It plays crucial roles in DNA replication initiation, DNA damage response, and replication stress response pathways. HELB is involved in homologous recombination regulation and has a significant impact on genome maintenance [1].

HELB is recruited to single-stranded DNA (ssDNA) by interacting with Replication Protein A (RPA) and inhibits DNA end resection by suppressing EXO1 and BLM-DNA2 nucleases, acting as a feedback inhibitor of the process [2]. A rare SNP (rs75770066) in HELB impairs its interaction with RPA, reducing its recruitment to DNA damage sites and increasing homologous recombination, potentially affecting age at natural menopause [4]. Exome sequencing has identified HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer [3,6]. In tropical cattle, missense mutations in HELB, which is involved in the DNA damage response, may have contributed to their adaptation to the harsh environment [5].

In conclusion, HELB is essential for genome maintenance, playing key roles in DNA replication, damage response, and recombination regulation. Studies using genetic models, such as those involving SNPs or in the context of disease-associated gene discovery, have revealed its significance in various biological processes and disease conditions like epithelial ovarian cancer and potentially in traits related to animal adaptation.

References:

1. Hazeslip, Lindsey, Zafar, Maroof Khan, Chauhan, Muhammad Zain, Byrd, Alicia K. 2020. Genome Maintenance by DNA Helicase B. In Genes, 11, . doi:10.3390/genes11050578. https://pubmed.ncbi.nlm.nih.gov/32455610/

2. Tkáč, Ján, Xu, Guotai, Adhikary, Hemanta, Masson, Jean-Yves, Durocher, Daniel. 2016. HELB Is a Feedback Inhibitor of DNA End Resection. In Molecular cell, 61, 405-418. doi:10.1016/j.molcel.2015.12.013. https://pubmed.ncbi.nlm.nih.gov/26774285/

3. Dicks, Ed M, Tyrer, Jonthan P, Ezquina, Suzana, Gayther, Simon A, Pharoah, Paul D P. 2024. Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer. In medRxiv : the preprint server for health sciences, , . doi:10.1101/2024.04.02.24304968. https://pubmed.ncbi.nlm.nih.gov/38633804/

4. Osei, Bertha, May, Benjamin H, Stiefel, Clara M, Enemark, Eric J, Byrd, Alicia K. 2024. Rare SNP in the HELB gene interferes with RPA interaction and cellular function of HELB. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.02.27.582415. https://pubmed.ncbi.nlm.nih.gov/38464108/

5. Naval-Sánchez, Marina, Porto-Neto, Laercio R, Cardoso, Diercles F, Kijas, James, Reverter, Antonio. 2020. Selection signatures in tropical cattle are enriched for promoter and coding regions and reveal missense mutations in the damage response gene HELB. In Genetics, selection, evolution : GSE, 52, 27. doi:10.1186/s12711-020-00546-6. https://pubmed.ncbi.nlm.nih.gov/32460767/

6. Dicks, Ed M, Tyrer, Jonthan P, Ezquina, Suzana, Gayther, Simon A, Pharoah, Paul D P. 2025. Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer. In European journal of human genetics : EJHG, 33, 297-303. doi:10.1038/s41431-025-01786-0. https://pubmed.ncbi.nlm.nih.gov/39939714/