Background: Rad17 is a key DNA damage response protein that undergoes ubiquitylation-mediated degradation. Results: USP20 is a deubiquitylase that interacts with and stabilizes Rad17 in a proteasome-dependent manner, and it is required for Chk1 phosphorylation. Conclusion: USP20 is a novel regulator of the DNA damage response. Significance: USP20 role sheds more light on the ubiquitylation events associated with DNA damage, and may predict chemotherapy response.

Identification of molecular markers of early‐stage breast cancer development is important for the diagnosis and prevention of the disease. In the present study, we used microarray analysis to examine the differential expression of genes in the rat mammary gland soon after treatment with a known chemical carcinogen, 7,12‐dimethylbenz[a]anthracene (DMBA), and prior to tumor development. Six weeks after DMBA, differential expression of multiple genes involved in cell growth, differentiation and microtubule dynamics were observed. Gene expression changes were further validated by a combination of techniques, including real‐time PCR, RT‐PCR, Western blotting and immunohistochemistry. An inhibition of differentiation in this early stage was suggested by the lower expression of β‐casein and transferrin and higher expression of hsp27 in glands from DMBA‐treated rats. Possible cell cycle deregulation was indicated by an increased expression of cyclin D1 and hsp86, a heat shock protein associated with cyclin D1. Prior to tumor development, DMBA increased cellular proliferation as detected by Ki‐67 and stathmin immunostaining in histologically normal mammary gland. Genes regulating microtubule function, including stathmin, Ran, α‐tubulin and hsp27, were all overexpressed in the mammary gland of DMBA‐treated rats, raising the possibility that disruption of microtubule dynamics and abnormal mitosis may be critical events preceding breast cancer development. Several of the altered proteins, including hsp27, hsp86 and stathmin, may ultimately serve as markers of early breast cancer development. Published 2005 Wiley‐Liss, Inc.

Background: hPso4 has been implicated in the resistance to interstrand cross-linking DNA-damaging agents. Results: hPso4 complex is involved in normal replication, and it has a role in DNA repair by homologous recombination through the regulation of DNA strand resection. Conclusion: hPso4 has a function in DNA double strand break repair by homologous recombination. Significance: hPso4 complex levels could predict sensitivity of cancer cells to PARP inhibitors.