Sex steroid hormones and DNA repair regulation: Implications on cancer treatment responses.

The role of sex steroid hormones (SSHs) has been shown to modulate cancer cytotoxic treatment sensitivity. Dysregulation of DNA repair associated with genomic instability, abnormal cell survival and not only promotes cancer progression but also resistance to cancer treatment. The three major SSHs, androgen, estrogen, and progesterone, have been shown to interact with several essential DNA repair components. The presence of androgens directly regulates key molecules in DNA double-strand break (DSB) repair. Estrogen can promote cell proliferation and DNA repair, allowing cancer cells to tolerate chemotherapy and radiotherapy. Information on the role of progesterone in DNA repair is limited: progesterone interaction with some DNA repair components has been identified, but the biological significance is still unknown. Here, we review the roles of how each SSH affects DNA repair regulation and modulates response to genotoxic therapies and discuss future research that can be beneficial when combining SSHs with cancer therapy. We also provide preliminary analysis from publicly available databases defining the link between progesterone/PR and DDRs & DNA repair regulation that plausibly contribute to chemotherapy response and breast cancer patient survival.

Photoacclimation to high-light stress in Chlamydomonas reinhardtii during conditional senescence relies on generating pH-dependent, high-quenching centres.

Microalgae can respond to long-term increases in light intensity by altering the concentration of photosynthetic complexes. Under active growth, the ability of Chlamydomonas reinhardtii to acclimate to excess light is dependent on cell division to reduce the concentration of photosynthetic complexes. But, in batch culture, cells eventually reach stationary phase where their ability to divide is limited; this should impact their capacity to undergo photoacclimation. Our goal is to dissect excess-light responses as cells approach stationary phase and to determine how the strategies of photoacclimation differ compared to cells in the exponential-growth phase. In this study, cultures exited exponential growth and transitioned into a declining growth phase (DGP), where cells continued a slow rate of growth for the next seven days in both low (LL) and high-light (HL). During this period, both cultures experience a conditional senescence-related decline in chlorophyll levels. Under HL, however, the senescing cultures have a rapid decline in PSII reaction centres, maintain a stable concentration of LHCII antenna, rapidly increase LHCSR levels, and have a sustained increase in Fo/Fm. Collectively this implies that the remaining antenna act as pH-dependent, quenching centres, presumably to protect the senescing chloroplast against HL. We discovered that acclimating to HL post-exponential phase involves active degradation that is intertwined with the normal senescence process that allowed for a limited rate of cell division.

Transcriptome Profiling of Bigelowiella natans in Response to Light Stress.

Bigelowiella natans is a marine chlorarachniophyte whose plastid was acquired secondarily via endosymbiosis with a green alga. During plastid evolution, the photosynthetic endosymbiont would have integrated with the host metabolic pathways. This would require the evolution and coordination of strategies to cope with changes in light intensity that includes changes in the expression of both endosymbiont and host-derived genes. To investigate the transcriptional response to light intensity in chlorarachniophytes, we conducted an RNA-seq experiment to identify differentially expressed genes following a 4-h shift to high or very-low light. A shift to high light altered the expression of over 2,000 genes, many involved with photosynthesis, PSII assembly, primary metabolism, and reactive-oxygen scavenging. These changes are an attempt to optimize photosynthesis and increase energy sinks for excess reductant, while minimizing photooxidative stress. A transfer to very-low light resulted in a lower photosynthetic performance and metabolic alteration, reflecting an energy-limited state. Genes located on the nucleomorph, the vestigial nucleus in the plastid, had few changes in expression in either light treatment, indicating this organelle has relinquished most transcriptional control to the nucleus. Overall, during plastid origin, both host and transferred endosymbiont genes evolved a harmonized transcriptional network to respond to a classic photosynthetic stress.

Evolution and regulation of Bigelowiella natans light-harvesting antenna system.

Bigelowiella natans is a mixotrophic flagellate and member of the chlorarachniophytes (Rhizaria), whose plastid is derived from a green algal endosymbiont. With the completion of the B. natans nuclear genome we are able to begin the analysis of the structure, function and evolution of the photosynthetic apparatus. B. natans has undergone substantial changes in photosystem structure during the evolution of the plastid from a green alga. While Photosystem II (PSII) composition is well conserved, Photosystem I (PSI) composition has undergone a dramatic reduction in accessory protein subunits. Coinciding with these changes, there was a loss of green algal LHCI orthologs while the PSII-like antenna system has the expected green algal-like proteins (encoded by genes Lhcbm1-8, Lhcb4). There are also a collection of LHCX-like proteins, which are commonly associated with stramenopiles and other eukaryotes with red-algal derived plastids, along with two other unique classes of LHCs- LHCY and LHCZ- whose function remains cryptic. To understand the regulation of the LHC gene family as an initial probe of function, we conducted an RNA-seq experiment under a short-term, high-light (HL) and low-light stress. The most abundant LHCII transcript (Lhcbm6) plus two other LHCBM types (Lhcbm1, 2) were down regulated under HL and up-regulated following a shift to very-low light (VL), as is common in antenna specializing in light harvesting. Many of the other LHCII and LHCY genes had a small, but significant increase in HL and most were only moderately affected under VL. The LHCX and LHCZ genes, however, had a strong up-regulation under HL-stress and most declined under VL, suggesting that they primarily have a role in photoprotection. This contrasts to the LHCY family that is only moderately responsive to light and a much higher basal level of expression, despite being within the LHCSR/LHCX clade. The expression of LHCX/Z proteins under HL-stress may be related to the induction of long-term, non-photochemical quenching mechanisms.