RAD52 resolves transcription-replication conflicts to mitigate R-loop induced genome instability.

Collisions of the transcription and replication machineries on the same DNA strand can pose a significant threat to genomic stability. These collisions occur in part due to the formation of RNA-DNA hybrids termed R-loops, in which a newly transcribed RNA molecule hybridizes with the DNA template strand. This study investigated the role of RAD52, a known DNA repair factor, in preventing collisions by directing R-loop formation and resolution.

HELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51.

DNA double-stranded breaks (DSBs) are deleterious lesions, and their incorrect repair can drive cancer development. HELQ is a superfamily 2 helicase with 3' to 5' polarity, and its disruption in mice confers germ cells loss, infertility and increased predisposition to ovarian and pituitary tumours. At the cellular level, defects in HELQ result in hypersensitivity to cisplatin and mitomycin C, and persistence of RAD51 foci after DNA damage.

Measuring nonhomologous end-joining, homologous recombination and alternative end-joining simultaneously at an endogenous locus in any transfectable human cell.

Double strand break (DSB) repair primarily occurs through 3 pathways: non-homologous end-joining (NHEJ), alternative end-joining (Alt-EJ), and homologous recombination (HR). Typical methods to measure pathway usage include integrated cassette reporter assays or visualization of DNA damage induced nuclear foci. It is now well understood that repair of Cas9-induced breaks also involves NHEJ, Alt-EJ, and HR pathways, providing a new format to measure pathway usage.

Capitalizing on Cancer Replication Stress by Preventing PAR Chain Turnover: A New Type of Synthetic Lethality.

Tumors resistant to PARP inhibitors frequently show signs of replication stress, with hyper-activated PARP. In this issue of Cancer Cell, Pillay et al. demonstrate that inhibiting PAR-chain turnover results in cell-cycle arrest, which is cytotoxic when combined with cell-cycle checkpoint inhibition and constitutes a novel cancer therapy.

Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway.

The Rad51 paralogs are required for homologous recombination (HR) and the maintenance of genomic stability. The molecular mechanisms by which the five vertebrate Rad51 paralogs regulate HR and genomic integrity remain unclear. The Rad51 paralogs associate with one another in two distinct complexes: Rad51B-Rad51C-Rad51D-XRCC2 (BCDX2) and Rad51C-XRCC3 (CX3).