FOXO3a and FOXM1 are two forkhead transcription factors with antagonistic roles in cancer and DNA damage response. FOXO3a functions like a typical tumour suppressor, whereas FOXM1 is a potent oncogene aberrantly overexpressed in genotoxic resistant cancers. FOXO3a not only represses FOXM1 expression but also its transcriptional output. Recent research has provided novel insights into a central ...

p53 plays a key role in regulating DNA damage response by suppressing cell cycle progression or inducing apoptosis depending on extent of DNA damage. However, it is not clear why mild genotoxic stress favors growth arrest, whereas excessive lesions signal cells to die. Here we showed that TAp73, a p53 homologue thought to have a similar function as p53, restrains the transcriptional activity of...

Biological model: In this project, we investigated the control of radiation-induced genotoxic damage expression in somatic cells of the nematode Caenorhabditis elegans. We measured genotoxic damage in the C. elegans intestine by irradiating young larvae with 20 intestinal cells. Fourteen of these cells undergo exactly one nuclear division without cytoplasmic division leading to 14 binucleate ce...

The basis of many anti-cancer therapies is the use of genotoxic agents that damage DNA and thus kill dividing cells. Agents that cause cells to override the DNA-damage checkpoint are predicted to sensitize cells to killing by genotoxic agents. They have therefore been sought as adjuncts in radiation therapy and chemotherapy. One such compound, caffeine, uncouples cell-cycle progression from the...

In this paper we propose that eukaryotic cells, under severe genotoxic stress, can commit genoautotomy (genome 'self-injury') that involves cutting and releasing single-strand DNA (ssDNA) fragments from double-stranded DNA and leaving ssDNA gaps in the genome. The ssDNA gaps could be easily and precisely repaired later. The released ssDNA fragments may play some role in the regulation of cell c...

Background: This study has used biomarker of exposure-effect continuum to examine the biological characteristics of organophosphate (OP) toxicity and its genotoxic effect among rice farmers. Materials and Methods: A cross-sectional study was conducted among 160 pesticide exposed rice farmers and 160 adults from the fishing village as the unexposed group. They share the common socio-economical ...

Williams-Beuren syndrome (WBS, no. OMIM 194050) is a rare multisystem genetic disorder caused by a microdeletion on chromosome 7q11.23 and characterized by cardiovascular malformations, mental retardation, and a specific facial dysmorphism. Recently, we reported that a series of non‑Hodgkin's lymphoma occurs in children with WBS and thus hypothesized that a predisposition to cancer may be assoc...

BACKGROUND Extensive DNA damage leads to apoptosis. Histones play a central role in DNA damage sensing and may mediate signals of genotoxic damage to cytosolic effectors including mitochondria. METHODOLOGY/PRINCIPAL FINDINGS We have investigated the effects of histones on mitochondrial function and membrane integrity. We demonstrate that both linker histone H1 and core histones H2A, H2B, H3, ...

Phosphoinositide 3-kinase related protein kinases (PIKK) including ataxia-telangiectasia mutated (ATM), DNAdependent protein kinase (DNA-PK), and ATM and Rad3-related (ATR) coordinate cellular responses to DNA damage. DNA-PK and ATM are primarily activated by double-strand breaks. The ATR kinase, in contrast, responds to numerous forms of genotoxic stress including intrastrand cross-links, oxid...

DNA repair is the first barrier in the defense against genotoxic stress. In recent years, mechanisms that recognize DNA damage and activate DNA repair functions through transcriptional upregulation and post-translational modification were the focus of intensive research. Most DNA repair pathways are complex, involving many proteins working in discrete consecutive steps. Therefore, their balance...