Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair.

Drugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, a meiotic protein in the synaptonemal complex, is aberrantly and commonly expressed in breast and ovarian cancers and associated with broad resistance to DDR drugs. Mechanistically, SYCP2 enhances the repair of DNA double-strand breaks (DSBs) through transcription-coupled homologous recombination (TC-HR). SYCP2 promotes R-loop formation at DSBs and facilitates RAD51 recruitment independently of BRCA1. SYCP2 loss impairs RAD51 localization, reduces TC-HR, and renders tumors sensitive to PARP and topoisomerase I (TOP1) inhibitors. Furthermore, our studies of two clinical cohorts find that SYCP2 overexpression correlates with breast cancer resistance to antibody-conjugated TOP1 inhibitor and ovarian cancer resistance to platinum treatment. Collectively, our data suggest that SYCP2 confers cancer cell resistance to DNA-damaging agents by stimulating R-loop-mediated DSB repair, offering opportunities to improve DDR therapy.

Size-Dependent Electrical Transport Properties in Conducting Diamond Nanostripes.

With the advances in nanofabrication technology, horizontally aligned and well-defined nitrogen-doped ultrananocrystalline diamond nanostripes can be fabricated with widths in the order of tens of nanometers. The study of the size-dependent electron transport properties of these nanostructures is crucial to novel electronic and electrochemical applications. In this paper, 100 nm thick n-type ultrananocrystalline diamond thin films were synthesized by microwave plasma-enhanced chemical vapor deposition method with 5% N2 gas in the plasma during the growth process. Then the nanostripes were fabricated using standard electron beam lithography and reactive ion etching techniques. The electrical transport properties of the free-standing single nanostripes of different widths from 75 to 150 nm and lengths from 1 to 128 µm were investigated. The study showed that the electrical resistivity of the n-type ultrananocrystalline diamond nanostripes increased dramatically with the decrease in the nanostripe width. The nanostripe resistivity was nearly doubted when the width was reduced from 150 nm to 75 nm. The size-dependent variability in conductivity could originate from the imposed diffusive scattering of the nanostripe surfaces which had a further compounding effect to reinforce the grain boundary scattering.