Enhancing low-dose radiotherapy efficacy with PARP inhibitors via FBL-mediated oxidative stress response in colorectal cancer.

The effectiveness of radiotherapy in colorectal cancer (CRC) relies on its ability to induce cell death via the generation of reactive oxygen species (ROS). However, genes responsible for mitigating oxidative stress can impede radiotherapy's efficacy. In this study, we elucidate a significant association between the nucleolar protein Fibrillarin (FBL) and the oxidative stress response in CRC tumors.

The transcription factor PAX5 activates human LINE1 retrotransposons to induce cellular senescence.

As a hallmark of senescent cells, the derepression of Long Interspersed Elements 1 (LINE1) transcription results in accumulated LINE1 cDNA, which triggers the secretion of the senescence-associated secretory phenotype (SASP) and paracrine senescence in a cGAS-STING pathway-dependent manner. However, transcription factors that govern senescence-associated LINE1 reactivation remain ill-defined. Here, we predict several transcription factors that bind to human LINE1 elements to regulate their transcription by analyzing the conserved binding motifs in the 5'-untranslated regions (UTR) of the commonly upregulated LINE1 elements in different types of senescent cells.

SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner.

Sirtuin 2 (SIRT2) regulates the maintenance of genome integrity by targeting pathways of DNA damage response and homologous recombination repair. However, whether and how SIRT2 promotes base excision repair (BER) remain to be determined. Here, we found that independent of its catalytic activity SIRT2 interacted with the critical glycosylase OGG1 to promote OGG1 recruitment to its own promoter upon oxidative stress, thereby enhancing OGG1 promoter activity and increasing BER efficiency.

Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair.

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with increasing incidence rates and high mortality rates. The currently available methods for treating HCC include surgery, radiotherapy or chemotherapy, but all of them have limitations. Therefore, developing novel therapeutic methods for HCC is in great need.

Activated or Impaired: An Overview of DNA Repair in Neurodegenerative Diseases.

As the population ages, age-related neurodegenerative diseases have become a major challenge in health science. Currently, the pathology of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, is still not fully understood. Remarkably, emerging evidence indicates a role of genomic DNA damage and repair in various neurodegenerative disorders.

Chrysin impairs genomic stability by suppressing DNA double-strand break repair in breast cancer cells.

Chrysin, a natural compound isolated from various plants, such as the blue passion flower (.), exhibits multiple pharmacological activities, such as antitumor, anti-inflammatory and antioxidant activities. Accumulating evidence shows that chrysin inhibits cancer cell growth by inducing apoptosis and regulating cell cycle arrest.

Diosmetin enhances the sensitivity of radiotherapy by suppressing homologous recombination in endometrial cancer.

Radiotherapy is an essential treatment for endometrial cancer (EC), especially in advanced, metastatic, and recurrent cases. Combining radiotherapy, which mainly causes DNA double-strand breaks (DSBs), with small molecules targeting aberrantly activated homologous recombination (HR) repair pathways holds great potential for treating ECs in advanced stages. Here, we demonstrate that diosmetin (DIO), a natural flavonoid, suppresses HR, therefore inhibiting cell proliferation and enhancing the sensitivity of EC to radiotherapy.

Rational combination therapy for hepatocellular carcinoma with PARP1 and DNA-PK inhibitors.

Understanding differences in DNA double-strand break (DSB) repair between tumor and normal tissues would provide a rationale for developing DNA repair-targeted cancer therapy. Here, using knock-in mouse models for measuring the efficiency of two DSB repair pathways, homologous recombination (HR) and nonhomologous end-joining (NHEJ), we demonstrated that both pathways are up-regulated in hepatocellular carcinoma (HCC) compared with adjacent normal tissues due to altered expression of DNA repair factors, including PARP1 and DNA-PKcs. Surprisingly, inhibiting PARP1 with olaparib abrogated HR repair in HCC.

Fight to the bitter end: DNA repair and aging.

DNA carries the genetic information that directs complex biological processes; thus, maintaining a stable genome is critical for individual growth and development and for human health. DNA repair is a fundamental and conserved mechanism responsible for mending damaged DNA and restoring genomic stability, while its deficiency is closely related to multiple human disorders. In recent years, remarkable progress has been made in the field of DNA repair and aging.

The deacetylase SIRT6 promotes the repair of UV-induced DNA damage by targeting DDB2.

The NAD+-dependent deacetylase and mono-ADP-ribosyl transferase SIRT6 stabilizes the genome by promoting DNA double strand break repair, thereby acting as a tumor suppressor. However, whether SIRT6 regulates nucleotide excision repair (NER) remains unknown. Here, we showed that SIRT6 was recruited to sites of UV-induced DNA damage and stimulated the repair of UV-induced DNA damage.

An HMGA2-p62-ERα axis regulates uterine leiomyomas proliferation.

Uterine leiomyomas (ULM) are a major public health issue contributing to high morbidity and poor pregnancy outcomes. However, its molecular pathogenesis is poorly understood. HMGA2-ULM is the second major subtype of human ULM and associates with large sizes, fast-growth, and high percentages of estrogen receptor α (ERα).

Base excision repair but not DNA double-strand break repair is impaired in aged human adipose-derived stem cells.

The decline in DNA repair capacity contributes to the age-associated decrease in genome integrity in somatic cells of different species. However, due to the lack of clinical samples and appropriate tools for studying DNA repair, whether and how age-associated changes in DNA repair result in a loss of genome integrity of human adult stem cells remains incompletely characterized. Here, we isolated 20 eyelid adipose-derived stem cell (ADSC) lines from healthy individuals (young: 10 donors with ages ranging 17-25 years; old: 10 donors with ages ranging 50-59 years).

A PARP1-BRG1-SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites.

Creating access to DNA double-strand break (DSB) sites in the chromatin context is an essential step during the repair process, but much remains to be determined about its regulatory mechanisms. Here, using a novel reporter cassette for simultaneous detection of homologous recombination (HR) and nonhomologous end joining (NHEJ) at the same chromosomal site, we report that the efficiency of HR but not NHEJ negatively correlates with nucleosome density. We demonstrate that PARP1 is required for HR by modulating nucleosome density at damage sites.

PdEPF1 regulates water-use efficiency and drought tolerance by modulating stomatal density in poplar.

Water deficiency is a critical environmental condition that is seriously reducing global plant production. Improved water-use efficiency (WUE) and drought tolerance are effective strategies to address this problem. In this study, PdEPF1, a member of the EPIDERMAL PATTERNING FACTOR (EPF) family, was isolated from the fast-growing poplar clone NE-19 [Populus nigra × (Populus deltoides × Populus nigra)].