OBJECTIVE To study the meiotic abnormalities during prophase I in an azoospermic man with t(1;21) reciprocal translocation. DESIGN Analysis of synapses, recombination, and transcription inactivation in a testicular biopsy sample. SETTING Research laboratory. PATIENT(S) One azoospermic patient with t(1;21) and five men with normal spermatogenesis. INTERVENTION(S) Immunostaining for SCP3,...

Eukaryotic cells employ a suite of replication and mitotic checkpoints to ensure the accurate transmission of their DNA. In budding yeast, both the DNA damage checkpoint and the spindle assembly checkpoint (SAC) block cells prior to anaphase. The presence of a single unrepaired double-strand break (DSB) activates ATR and ATM protein kinase homologs Mec1 and Tel1, which then activate downstream ...

JMJD2C is a candidate oncogene that encodes a histone lysine demethylase with the ability to demethylate the lysine 9 residue of histone H3 (H3K9). The expression levels of JMJD2C are associated with tumor development and clinical outcome. Here we identify JMJD2C as a new substrate for caspase-3. JMJD2C is cleaved by caspase-3 at DEVD396G motif and then loses its demethylase activity. Additiona...

Glucocorticoids (GCs), which act on stress pathways, are well-established in the co-treatment of different kinds of tumors; however, the underlying mechanisms by which GCs act are not yet well elucidated. As such, this work investigates the role of glucocorticoids, specifically dexamethasone (DEXA), in the processes referred to as DNA damage and DNA damage response (DDR), establishing a new app...

Vpr, the viral protein R of human immunodeficiency virus type 1, induces G(2) cell cycle arrest and apoptosis in mammalian cells via ATR (for "ataxia-telangiectasia-mediated and Rad3-related") checkpoint activation. The expression of Vpr induces the formation of the gamma-histone 2A variant X (H2AX) and breast cancer susceptibility protein 1 (BRCA1) nuclear foci, and a C-terminal domain is requ...

Loss-of-function mutations in the human RecQ helicase genes WRN and BLM respectively cause the genetic instability/cancer predisposition syndromes Werner syndrome and Bloom syndrome. To identify common and unique functions of WRN and BLM, we systematically analyzed cell proliferation, cell survival, and genomic damage in isogenic cell lines depleted of WRN, BLM, or both proteins. Cell prolifera...

A group of histone deacetylase (HDAC) inhibitors has been shown to suppress the growth of a variety of human tumor lines in vitro and in vivo and they are among the most promising candidates for anti-cancer therapeutic agents. We investigated the ability of scriptaid, a novel HDAC inhibitor and trichostatin A (TSA) to enhance cell killing by radiation in radioresistant SQ-20B cells derived from...

Telomere shortening in normal human cells causes replicative senescence, a p53-dependent growth arrest state, which is thought to represent an innate defence against tumour progression. However, although it has been postulated that critical telomere loss generates a 'DNA damage' signal, the signalling pathway(s) that alerts cells to short dysfunctional telomeres remains only partially defined. ...

PURPOSE To examine the effects of combined blockade of DNA-dependent protein kinase (DNA-PK) and poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) on accelerated senescence in irradiated H460 and A549 non-small cell lung cancer cells. METHODS AND MATERIALS The effects of KU5788 and AG014699 (inhibitors of DNA-PK and PARP-1, respectively) on clonogenic survival, DNA double-strand breaks...

DNA double-strand breaks (DSBs) are generally accepted to be the most biologically significant lesion by which ionizing radiation causes cancer and hereditary disease. However, no information on the induction and processing of DSBs after physiologically relevant radiation doses is available. Many of the methods used to measure DSB repair inadvertently introduce this form of damage as part of th...