Editorial Material
Biochemistry & Molecular Biology
Ilona Faustova, Mart Loog
Summary: Study by Hossain et al. (2021) reveals that ORC1 and CDC6 interact during pre-replicative complex formation in G1, mediated by SLiMs in IDRs and regulated by CDKs.
Article
Biochemistry & Molecular Biology
Jian Li, Jiangqing Dong, Weitao Wang, Daqi Yu, Xinyu Fan, Yan Chit Hui, Clare S. K. Lee, Wai Hei Lam, Nathan Alary, Yang Yang, Yingyi Zhang, Qian Zhao, Chun-Long Chen, Bik-Kwoon Tye, Shangyu Dang, Yuanliang Zhai
Summary: In eukaryotes, the assembly and activation of the MCM2-7 double hexamer (DH) is required for DNA replication initiation. The mechanism for the initial melting of DNA strands is unknown. This study presents the cryo-electron microscopy structure of the human MCM-DH, revealing that it untwists and stretches the DNA strands to create an initial open structure (IOS) at the hexamer junction. The disruption of IOS inhibits DH formation and replication initiation. The mapping of hMCM-DH footprints suggests that IOSs are distributed across the genome, aligning with initiation zones for stochastic origin firing.
Article
Biochemistry & Molecular Biology
Lilas Courtot, Elodie Bournique, Chrystelle Maric, Laure Guitton-Sert, Miguel Madrid-Mencia, Vera Pancaldi, Jean-Charles Cadoret, Jean-Sebastien Hoffmann, Valerie Bergoglio
Summary: This study reveals that low replication stress can lead to advanced DNA replication timing, which is cell-type specific and involves large heterochromatin domains. These advanced events can be inherited by the next generation of cells, leading to changes in chromatin accessibility, replication origin landscape, and gene expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Chao Li, Yong-Peng Tan, Xue-Shan Ma, Zhen-Bo Wang, Tie-Gang Meng, Qing-Yuan Sun
Summary: This study investigated the roles of CDT1 and MCM2 in oocyte meiotic maturation and early embryonic development. The results showed that CDT1 is the major regulator of DNA replication, while MCM2 has no effect on oocyte meiotic maturation. The degradation of CDT1 is essential for preventing DNA re-replication in zygotes.
CELL PROLIFERATION
(2023)
Article
Biochemistry & Molecular Biology
Yoshito Abe, Yohei Ikeda, Saki Fujiyama, R. Manjunatha Kini, Tadashi Ueda
Summary: This study confirmed the importance of His26 in PriB for replication restart using plasmid complementation and examined the structure of the PriB-DnaT complex through NMR analysis. By evaluating the PriB-DnaT peptide complex model prepared by in silico docking and molecular dynamic simulation, a structural model was proposed that sheds light on the PriB-DnaT interaction.
Editorial Material
Cell Biology
Jean-Sebastien Hoffmann
Summary: The major challenge in DNA replication is to ensure the transmission of intact genetic material to daughter cells. Despite extensive research on the cellular responses to replication problems and their source, the transmission of genome modifications and their heritability in mitosis has been less documented. Recent studies have shown that low replication stress can impact the next generation of cells, transmitting DNA damage and altering the replication timing program of chromosomal domains in daughter cells. This progression of replication issues into mitosis and daughter cells may provide advantages by alerting cells to risky loci and offering an adaptive mechanism to anticipate future problems, especially in the context of cancer cell resistance to therapy.
Article
Biochemistry & Molecular Biology
Yixi Chen, Gaochun Wu, Chuanqi Wang, Huimin Zhang, Jinghua Zhu, Yueling Zhang, Zhongyang Lin, Defu Yao
Summary: The immediate-early (IE) protein IE1 of white spot syndrome virus (WSSV) acts as a transcription factor and modulates the host DNA replication machinery to support viral replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sayoko Sanada, Masashi Maekawa, Sota Tate, Hiroki Nakaoka, Yasuhiro Fujisawa, Koji Sayama, Shigeki Higashiyama
Summary: In this study, the cellular functions of wild-type SPOP in non-cancerous human keratinocyte-derived HaCaT cells were evaluated. SPOP knockdown resulted in reduced cell growth and arrested cell cycles at G1/S phase. The downregulation of DNA replication licensing factors CDT1 and CDC6 and the subsequent induction of p21 expression without p53 activation were observed upon SPOP knockdown. These results highlight the importance of SPOP in DNA replication licensing in non-cancerous keratinocyte HaCaT cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Jian Ma, Qing Shi, Gaofeng Cui, Haoyue Sheng, Maria Victoria Botuyan, Yingke Zhou, Yuqian Yan, Yundong He, Liguo Wang, Yuzhuo Wang, Georges Mer, Dingwei Ye, Chenji Wang, Haojie Huang
Summary: The study reveals that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP plays a crucial role in preventing DNA replication over-firing and genome instability by affecting Geminin ubiquitination. Mutations in SPOP may lead to replication origin over-firing, replication stress, and cell death, suggesting potential susceptibility to ATR inhibitor therapy in SPOP-mutated tumors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Fiona Jenkinson, Kang Wei Tan, Barbara Schopf, Miguel M. Santos, Philip Zegerman
Summary: In eukaryotes, cyclin-dependent kinase (CDK) inhibits helicase loading factors to ensure the exact duplication of the genome. CDK activates origin firing by phosphorylating Sld2 and Sld3, forming a transient intermediate called the pre-initiation complex (pre-IC). In yeast, the CDK phosphorylations of Sld3 and Sld2 are rapidly turned over by the phosphatases PP2A and PP4 during S phase. This dephosphorylation is important for genome-wide origin firing, pre-IC formation, and maintaining Sld3 dephosphorylation in G1 phase. PP2ARts1 specifically targets Sld3 and its dephosphorylation is critical for replication and cell viability.
Review
Biochemistry & Molecular Biology
Hui Zhang
Summary: DNA replication licensing is tightly regulated in eukaryotic cells to ensure proper replication initiation and prevent re-replication, with key mechanisms involving degradation of Cdt1 protein by CRL4(Cdt2) ubiquitin E3 ligase. The interaction between Cdt1 and PCNA, facilitated by the PIP box domain, plays a crucial role in this process, highlighting the importance of regulating DNA replication and genome stability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Hsiang-Chen Chou, Kuhulika Bhalla, Osama El Demerdesh, Olaf Klingbeil, Kaarina Hanington, Sergey Aganezov, Peter Andrews, Habeeb Alsudani, Kenneth Chang, Christopher R. Vakoc, Michael C. Schatz, W. Richard McCombie, Bruce Stillman
Summary: Each subunit of ORC and CDC6 is essential in human cells, with their deficiency leading to difficulties in DNA replication initiation and cell division cycle progression, as well as abnormal nuclear and cell morphology.
Article
Biochemistry & Molecular Biology
Beate Bersch, Nicolas Tarbouriech, Wim P. Burmeister, Frederic Iseni
Summary: Poxviruses are enveloped viruses with a linear, double-stranded DNA genome, and viral DNA synthesis is achieved by a DNA polymerase holoenzyme composed of three essential proteins. The catalytic subunit E9 forms a complex with the heterodimeric processivity factor made up of D4 and A20, which have a specific interaction involving a poxvirus-specific insertion. The interface between E9 and A20 comprises conserved hydrophobic residues and has been structurally characterized, providing insights into their molecular interactions.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Haiqing Fu, Christophe E. Redon, Bhushan L. Thakur, Koichi Utani, Robin Sebastian, Sang-Min Jang, Jacob M. Gross, Sara Mosavarpour, Anna B. Marks, Sophie Z. Zhuang, Sarah B. Lazar, Mishal Rao, Shira T. Mencer, Adrian M. Baris, Lorinc S. Pongor, Mirit I. Aladjem
Summary: Safeguards against excess DNA replication are often dysregulated in cancer cells, leading researchers to investigate the DNA synthesis patterns in cancer cells undergoing partial genome re-replication. The study reveals that re-replication in cancer cells results in aberrant replication fork dynamics and a skewed distribution of replication initiation, causing over-duplication in early-replicating genomic regions.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Ukhyun Jo, Yasuhisa Murai, Sirisha Chakka, Lu Chen, Ken Cheng, Junko Murai, Liton Kumar Saha, Lisa M. Miller Jenkins, Yves Pommier
Summary: Inactivation of Schlafen-11 (SLFN11) confers chemoresistance in cancer cells, but targeting the ATR pathway can overcome this resistance, revealing a potential therapeutic strategy. By identifying therapeutic targets and molecular mechanisms underlying chemoresistance, we have demonstrated that ATR inhibition can sensitize SLFN11-deficient cancers to chemotherapy, providing new insights into cancer treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)