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Two ZNF509 (ZBTB49) isoforms induce cell-cycle arrest by activating transcription of p21/CDKN1A and RB upon exposure to genotoxic stress

01.02.2015 | Bu-Nam Jeon; Min-Kyeong Kim; Jae-Hyeon Yoon; Min-Young Kim; Haemin An; Hee-Jin Noh; Won-Il Choi; Dong-In Koh; Man-Wo ..., Nucleic Acids Research, 2015

ZNF509 is unique among POK family proteins in that four isoforms are generated by alternative splicing. Short ZNF509 (ZNF509S1, -S2 and -S3) isoforms contain one or two out of the seven zinc-fingers contained in long ZNF509 (ZNF509L). Here, we investigated the functions of ZNF509 isoforms in ...


Replication stress by Py–Im polyamides induces a non-canonical ATR-dependent checkpoint response

01.02.2015 | Thomas F. Martínez; John W. Phillips; Kenneth K. Karanja; Piotr Polaczek; Chieh-Mei Wang; Benjamin C. Li; Judith L. ..., Nucleic Acids Research, 2015

Pyrrole–imidazole polyamides targeted to the androgen response element were cytotoxic in multiple cell lines, independent of intact androgen receptor signaling. Polyamide treatment induced accumulation of S-phase cells and of PCNA replication/repair foci. Activation of a cell cycle checkpoint ...


A gemcitabine sensitivity screen identifies a role for NEK9 in the replication stress response

01.02.2015 | Scott C. Smith; Aleksandra V. Petrova; Matthew Z. Madden; Hongyan Wang; Yunfeng Pan; Matthew D. Warren; Claire W. Ha ..., Nucleic Acids Research, 2015

The Replication Stress Response (RSR) is a signaling network that recognizes challenges to DNA replication and coordinates diverse DNA repair and cell-cycle checkpoint pathways. Gemcitabine is a nucleoside analogue that causes cytotoxicity by inducing DNA replication blocks. Using a synthetic ...


FBXL5-mediated degradation of single-stranded DNA-binding protein hSSB1 controls DNA damage response

01.02.2015 | Zhi-Wei Chen; Bin Liu; Nai-Wang Tang; Yun-Hua Xu; Xiang-Yun Ye; Zi-Ming Li; Xiao-Min Niu; Sheng-Ping Shen; Shun Lu; ..., Nucleic Acids Research, 2015

Human single-strand (ss) DNA binding proteins 1 (hSSB1) has been shown to participate in DNA damage response and maintenance of genome stability by regulating the initiation of ATM-dependent signaling. ATM phosphorylates hSSB1 and prevents hSSB1 from ubiquitin-proteasome-mediated degradation. ...


Probing the elastic limit of DNA bending

01.12.2014 | Tung T. Le; Harold D. Kim, Nucleic Acids Research, 2014

Sharp bending of double-stranded DNA (dsDNA) plays an essential role in genome structure and function. However, the elastic limit of dsDNA bending remains controversial. Here, we measured the opening rates of small dsDNA loops with contour lengths ranging between 40 and 200 bp using ...


Mycobacterium RbpA cooperates with the stress-response {sigma}B subunit of RNA polymerase in promoter DNA unwinding

01.12.2014 | Yangbo Hu; Zakia Morichaud; Ayyappasamy Sudalaiyadum Perumal; Françoise Roquet-Baneres; Konstantin Brodolin, Nucleic Acids Research, 2014

RbpA, a transcriptional activator that is essential for Mycobacterium tuberculosis replication and survival during antibiotic treatment, binds to RNA polymerase (RNAP) in the absence of promoter DNA. It has been hypothesized that RbpA stimulates housekeeping gene expression by promoting assembly ...


Binding of the transcription factor Atf1 to promoters serves as a barrier to phase nucleosome arrays and avoid cryptic transcription

01.12.2014 | Patricia García; Esther Paulo; Jun Gao; Wayne P. Wahls; José Ayté; Ernesto Lowy; Elena Hidalgo, Nucleic Acids Research, 2014

Schizosaccharomyces pombe displays a large transcriptional response common to several stress conditions, regulated primarily by the transcription factor Atf1. Atf1-dependent promoters contain especially broad nucleosome depleted regions (NDRs) prior to stress imposition. We show here that basal ...


Genome-wide mapping of unexplored essential regions in the Saccharomyces cerevisiae genome: evidence for hidden synthetic lethal combinations in a genetic interaction network

01.11.2014 | Saeed Kaboli; Takuya Yamakawa; Keisuke Sunada; Tao Takagaki; Yu Sasano; Minetaka Sugiyama; Yoshinobu Kaneko; Satoshi ..., Nucleic Acids Research, 2014

Despite systematic approaches to mapping networks of genetic interactions in Saccharomyces cerevisiae, exploration of genetic interactions on a genome-wide scale has been limited. The S. cerevisiae haploid genome has 110 regions that are longer than 10 kb but harbor only non-essential genes. ...


Double-strand break repair deficiency in NONO knockout murine embryonic fibroblasts and compensation by spontaneous upregulation of the PSPC1 paralog

01.11.2014 | Shuyi Li; Zhentian Li; Feng-Jue Shu; Hairong Xiong; Andrew C. Phillips; William S. Dynan, Nucleic Acids Research, 2014

NONO, SFPQ and PSPC1 make up a family of proteins with diverse roles in transcription, RNA processing and DNA double-strand break (DSB) repair. To understand long-term effects of loss of NONO, we characterized murine embryonic fibroblasts (MEFs) from knockout mice. In the absence of genotoxic ...


Folliculin (Flcn) inactivation leads to murine cardiac hypertrophy through mTORC1 deregulation

01.11.2014 | Yukiko Hasumi; Masaya Baba; Hisashi Hasumi; Ying Huang; Martin Lang; Rachel Reindorf; Hyoung-bin Oh; Sebastiano Scia ..., Human Molecular Genetics, 2014

Cardiac hypertrophy, an adaptive process that responds to increased wall stress, is characterized by the enlargement of cardiomyocytes and structural remodeling. It is stimulated by various growth signals, of which the mTORC1 pathway is a well-recognized source. Here, we show that loss of Flcn, a ...


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