The Involvement of Acidic Nucleoplasmic DNA-binding Protein (And-1) in the Regulation of Prereplicative Complex (pre-RC) Assembly in Human Cells

Li, Yongming; Xiao, Haijie; Renty, Christelle de; Jaramillo-Lambert, Aimee; Han, Zhiyong; DePamphilis, Melvin L.; Brown, Kristy J.; Zhu, Wenge

doi:10.1074/jbc.m112.404277

Cited by 17 publications

(25 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the established cellular function is pre-RC activation for DNA synthesis, WDHD1 has also been implicated in a role in pre-RC assembly, functioning as a DNA replication initiation factor (19). The known DNA replication initiation factors, Cdt1 and Cdc6, have been shown to be required for rereplication (9,10,14,34,44,63).…”

Section: Discussionmentioning

confidence: 99%

“…HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription, and replication. In addition to its established role in pre-RC activation (19)(20)(21), WDHD1 is also involved in pre-RC assembly (19). The WDHD1 gene is localized adjacent to replication foci, interacts with human primase-DNA polymerase/MCM10, and is required for DNA synthesis (20,22,23).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional Profiling of E7-Expressing Cells

Yang

Zhang

Gao

et al. 2016

J Virol

View full text Add to dashboard Cite

The E7 oncoprotein of the high-risk human papillomavirus (HPV) plays a major role in HPV-induced carcinogenesis. E7 abrogates the G 1 cell cycle checkpoint and induces genomic instability, but the mechanism is not fully understood. In this study, we performed RNA sequencing (RNA-seq) to characterize the transcriptional profile of keratinocytes expressing HPV 16 (HPV-16) E7. At the transcriptome level, 236 genes were differentially expressed between E7 and vector control cells. A subset of the differentially expressed genes, most of them novel to E7-expressing cells, was further confirmed by real-time PCR. Of interest, the activities of multiple transcription factors were altered in E7-expressing cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were investigated. The upregulated genes were enriched in cell cycle and DNA replication, as well as in the DNA metabolic process, transcription, DNA damage, DNA repair, and nucleotide metabolism. Specifically, we focused our studies on the gene encoding WDHD1 (WD repeat and high mobility group [HMG]-box DNA-binding protein), one of the genes that was upregulated in E7-expressing cells. WDHD1 is a component of the replisome that regulates DNA replication. Recent studies suggest that WDHD1 may also function as a DNA replication initiation factor as well as a G 1 checkpoint regulator. We found that in E7-expressing cells, the steady-state level of WDHD1 protein was increased along with the half-life. Moreover, downregulation of WDHD1 reduced E7-induced G 1 checkpoint abrogation and rereplication, demonstrating a novel function for WDHD1. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications. IMPORTANCEThe high-risk HPV types induce cervical cancer and encode an E7 oncoprotein that plays a major role in HPV-induced carcinogenesis. However, the mechanism by which E7 induces carcinogenesis is not fully understood; specific anti-HPV agents are not available. In this study, we performed RNA-seq to characterize transcriptional profiling of keratinocytes expressing HPV-16 E7 and identified more than 200 genes that were differentially expressed between E7 and vector control cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were identified. Significantly, the WDHD1 gene, one of the genes that is upregulated in E7-expressing cells, was found to play an important role in E7-induced G 1 checkpoint abrogation and rereplication. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications. H uman papillomaviruses (HPVs) are small DNA viruses that replicate in squamous epithelia. Specific types of HPV (highrisk HPVs) are the causative agents for cervical and several other cancers (1). The transforming properties of high-risk HPVs such as HPV 16 (HPV-16) primarily depend on E7 as well as E6 oncogenes (1, 2). HPV E6 and E7 proteins promote the degradation of p53 and pRb, respectively (3, 4). E7 from the high-risk...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional Profiling of E7-Expressing Cells

Yang

Zhang

Gao

et al. 2016

J Virol

View full text Add to dashboard Cite

show abstract

“…Silver staining was carried out with the SilverQuest TM silver staining kit (Invitrogen). Mass spectrometry was performed as described earlier (Li et al, 2012b).…”

Section: Plasmids and Antibodiesmentioning

confidence: 99%

“…Previous studies by others and us showed that the acidic nucleoplasmic DNA-binding protein 1 (And-1) is a replisome component and is required for efficient DNA replication in unperturbed cells (Zhu et al, 2007;Errico et al, 2009;Gambus et al, 2009;Im et al, 2009;Yoshizawa-Sugata & Masai, 2009;Bermudez et al, 2010;Li et al, 2012b). Ctf4/Mcl1, the ortholog of And-1 in yeast, is required for chromosome transmission fidelity, sister chromatin cohesion, DNA damage repair, maintenance of genome integrity, and the regulation of telomere replication (Kouprina et al, 1992;Hanna et al, 2001;Williams & McIntosh, 2002;Mayer et al, 2004;Tsutsui et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Ctf4/Mcl1, the ortholog of And-1 in yeast, is required for chromosome transmission fidelity, sister chromatin cohesion, DNA damage repair, maintenance of genome integrity, and the regulation of telomere replication (Kouprina et al, 1992;Hanna et al, 2001;Williams & McIntosh, 2002;Mayer et al, 2004;Tsutsui et al, 2005). Recent studies indicate that And-1 interacts with Tipin in Xenopus egg extracts and with Claspin in human cells (Errico et al, 2009;Li et al, 2012b), suggesting that And-1 may regulate DNA replication checkpoint activation in response to replication stress. This hypothesis is consistent with the effects of siRNA suppression of And-1 in human cells (Yoshizawa-Sugata & Masai, 2009), even though attempts to elucidate the mechanism by which And-1 affects the DNA damage response yielded inconclusive results (Yoshizawa-Sugata & Masai, 2009).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

And‐1 coordinates with Claspin for efficient Chk1 activation in response to replication stress

Hao

Renty

et al. 2015

The EMBO Journal

Self Cite

View full text Add to dashboard Cite

The replisome is important for DNA replication checkpoint activation, but how specific components of the replisome coordinate with ATR to activate Chk1 in human cells remains largely unknown. Here, we demonstrate that And-1, a replisome component, acts together with ATR to activate Chk1. And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR. Significantly, And-1 binds directly to ssDNA and facilitates the association of Claspin with ssDNA. Furthermore, And-1 associates with replication forks and is required for the recovery of stalled forks. These studies establish a novel ATR-And-1 axis as an important regulator for efficient Chk1 activation and reveal a novel mechanism of how the replisome regulates the replication checkpoint and genomic stability.

show abstract

Targeted inhibition of acidic nucleoplasmic DNA-binding protein 1 enhances radiosensitivity of non-small cell lung cancer

Gou

et al. 2022

Cancer Letters

View full text Add to dashboard Cite

The Involvement of Acidic Nucleoplasmic DNA-binding Protein (And-1) in the Regulation of Prereplicative Complex (pre-RC) Assembly in Human Cells

Cited by 17 publications

References 46 publications

Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional Profiling of E7-Expressing Cells

Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional Profiling of E7-Expressing Cells

And‐1 coordinates with Claspin for efficient Chk1 activation in response to replication stress

Targeted inhibition of acidic nucleoplasmic DNA-binding protein 1 enhances radiosensitivity of non-small cell lung cancer

Contact Info

Product

Resources

About