Article
Multidisciplinary Sciences
Xingxuan Wu, Shibin Xu, Peipei Wang, Zhao-Qi Wang, Hongxiang Chen, Xingzhi Xu, Bin Peng
Summary: ASPM plays a dispensable role in DNA replication but is enriched at stalled replication forks under replication stress. It promotes the loading of RAD9 and TopBP1 onto chromatin, facilitating ATR-CHK1 activation and ensuring genome stability.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Joanne Saldanha, Julie Rageul, Jinal A. Patel, Hyungjin Kim
Summary: DNA replication is a tightly controlled process that ensures the faithful duplication of the genome. DNA damage, both endogenous and exogenous, can cause replication stress, which needs to be protected and repaired to maintain genomic integrity and cell survival. The plasticity of the replication fork and the activation of the ATR kinase play crucial roles in overcoming replication obstacles and coordinating cellular responses to replication stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Jinal A. Patel, Hyungjin Kim
Summary: Accurate replication of the genome is crucial for cellular survival and tumor prevention. The DNA replication fork is susceptible to DNA lesions and damages that hinder its progression, leading to genome instability and tumorigenesis. The fork protection complex (FPC), particularly TIMELESS (TIM), plays a vital role in safeguarding the integrity of both active and stalled replication forks. Understanding TIM's multifaceted functions in DNA replication and stalled fork protection, as well as its collaboration with other genome surveillance factors, provides insights for potential therapies targeting replication vulnerability in cancer cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Genetics & Heredity
Yuchen Guo, Jun Wang, Bente Benedict, Chen Yang, Frank van Gemert, Xuhui Ma, Dongmei Gao, Hui Wang, Shu Zhang, Cor Lieftink, Roderick L. Beijersbergen, Hein Te Riele, Xiaohang Qiao, Qiang Gao, Chong Sun, Wenxin Qin, Rene Bernards, Cun Wang
Summary: This study identified ATR-CHK1 signaling as a therapeutic target for liver cancer. Pharmacological inhibition of ATR or CHK1 leads to proliferation inhibition in liver cancer cells with high replication stress levels. CDC7 inhibitors induce DNA replication stress in cells resistant to ATR or CHK1 inhibition, showing strong synergy with ATR or CHK1 inhibitors.
Article
Multidisciplinary Sciences
Katrina Montales, Kenna Ruis, Howard Lindsay, W. Matthew Michael
Summary: ATR kinase is activated by DNA damage and replication stress, but recruitment to damage sites is not sufficient for activation. TOPBP1 is transiently present at DSBs and its recruitment is influenced by MRN, CtIP, and ATM. The 9-1-1 complex and MDC1 are not essential for TOPBP1 recruitment to DSBs.
Article
Multidisciplinary Sciences
Kathleen Ho, Hongwei Luo, Wei Zhu, Yi Tang
Summary: This study reveals the critical role of SMG7 in the activation of the ATR-CHK1 axis, promoting CHK1 activation through interaction with RAD17, and controlling orderly cell cycle progression by maintaining CHK1 activity.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Xiaosong Hu, Dakun Pei, Mingxin Ci, Guanghui Zhang, Benqin Li, Jie Wang, Yue Shen, Xuan Zhai, Ping Liang, Hongjuan Cui
Summary: This study identifies ACTL6A as a critical regulator of DNA replication in glioblastoma, showing that ACTL6A knockdown impairs DNA replication initiation and induces DNA damage and apoptosis. ACTL6A transcriptionally regulates MCM5 expression and diminishes the activity of the ATR-Chk1 pathway.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Patrycja Gralewska, Arkadiusz Gajek, Dorota Rybaczek, Agnieszka Marczak, Aneta Rogalska
Summary: This study investigated the short-term efficacy of PARP inhibitor treatment on the DNA damage response pathway mediated by ATR and CHK1 kinases in BRCA(MUT) and BRCA(WT) cells. The combination of ATRi/CHK1i with PARPi did not have increased cytotoxicity. The combination of olaparib with ATR/CHK1 inhibitors generated chromosomal abnormalities and micronuclei. ATR/CHK1 inhibitors reduced BrdU incorporation and caused cell death.
Article
Biochemistry & Molecular Biology
Yoshitami Hashimoto, Hirofumi Tanaka
Summary: The study investigated the restart of stalled replication forks during mitosis using Xenopus egg extracts. Stalled forks could restart before nuclear envelope breakdown with excess dCTP, but efficiency decreased after NEB. The timing of NEB was delayed by ongoing forks rather than stalled forks, dependent on Wee1/Myt1 kinase activities.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Andreas Panagopoulos, Matthias Altmeyer
Summary: Cell cycle checkpoints play a crucial role in ensuring ordered progression between cell cycle phases, signaling cell stress and DNA damage, and halting cell cycle progression in the face of severe problems. Recent research indicates that cells respond to natural challenges such as replication impediments with more subtle and sophisticated mechanisms, utilizing fine-tuned deceleration and brake release controlled by ATR and CHK1. This reveals a more flexible adaptation of the cell cycle program to changing conditions.
TRENDS IN BIOCHEMICAL SCIENCES
(2021)
Article
Biology
Weihang Chai, Megan Chastain, Olga Shiva, Yuan Wang
Summary: The intrinsically disordered region (IDR) in the OB domain of STN1 plays a crucial role in modulating CST function in protecting genome stability under replication stress. Variants and mutations in this IDR cause genome instabilities, reduced viability, and increased sensitivity to replication stress, highlighting the importance of the IDR in regulating CST function in genome stability maintenance.
Review
Cell Biology
Shan Qiu, Guixing Jiang, Liping Cao, Jun Huang
Summary: Replication fork reversal is a critical protective mechanism in higher eukaryotic cells in response to replication stress, where forks change direction to form a Holliday junction-like structure for protection, with DNA damage repair proteins playing important roles.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Medicine, Research & Experimental
Salman Ahmed, Waqas Alam, Michael Aschner, Khalaf F. Alsharif, Ashraf Albrakati, Luciano Saso, Haroon Khan
Summary: Cancer is a severe medical condition causing millions of deaths each year, and chemotherapy and radiotherapy, although commonly used, have adverse health effects. Natural products targeting ATR-CHK1, essential components of DNA damage signaling and repair pathways, have shown potential in anti-cancer treatment and synergistic effects when combined with other drugs.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Oncology
Ioan T. Bold, Ann-Kathrin Specht, Conrad F. Droste, Alexandra Zielinski, Felix Meyer, Till S. Clauditz, Adrian Muenscher, Stefan Werner, Kai Rothkamm, Cordula Petersen, Kerstin Borgmann
Summary: Functional aneuploidy determined by CIN70 score influences prognosis through the expression of DNA repair proteins. Higher CIN70 scores are associated with increased expression of DNA repair proteins, specifically those involved in DNA replication and repair, which are related to survival. It is the balanced expression and coordinated activation of signaling cascades, rather than individual DNA repair proteins, that determines resistance to therapy.
Article
Multidisciplinary Sciences
Qian Zhu, Qiaoyan Yang, Xiaopeng Lu, Hui Wang, Lili Tong, Zheng Li, Ge Liu, Yantao Bao, Xingzhi Xu, Luo Gu, Jian Yuan, Xiangyu Liu, Wei-Guo Zhu
Summary: The study found that H3K14 trimethylation enhances ATR activation by recruiting the RPA complex to chromatin, thus facilitating the response to replication stress. Increased levels of H3K14me3 make cells more sensitive to replication stress, affecting cell cycle progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Janet Holden, Elaine M. Taylor, Howard D. Lindsay
Article
Multidisciplinary Sciences
Thomas A. Guilliam, Nigel C. Brissett, Aaron Ehlinger, Benjamin A. Keen, Peter Kolesar, Elaine M. Taylor, Laura J. Bailey, Howard D. Lindsay, Walter J. Chazin, Aidan J. Doherty
NATURE COMMUNICATIONS
(2017)
Article
Genetics & Heredity
Limei Ju, Jonathan Wing, Elaine Taylor, Renata Brandt, Predrag Slijepcevic, Marion Horsch, Birgit Rathkolb, Ildiko Racz, Lore Becker, Wolfgang Hans, Thure Adler, Johannes Beckers, Jan Rozman, Martin Klingenspor, Eckhard Wolf, Andreas Zimmer, Thomas Klopstock, Dirk H. Busch, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabe de Angelis, Gilbertus van der Horst, Alan R. Lehmann
Article
Biochemistry & Molecular Biology
Julie Bianchi, Sean G. Rudd, Stanislaw K. Jozwiakowski, Laura J. Bailey, Violetta Soura, Elaine Taylor, Irena Stevanovic, Andrew J. Green, Travis H. Stracker, Howard D. Lindsay, Aidan J. Doherty
Article
Biochemistry & Molecular Biology
Elaine M. Taylor, Sophie M. Cecillon, Antonio Bonis, J. Ross Chapman, Lawrence F. Povirk, Howard D. Lindsay
NUCLEIC ACIDS RESEARCH
(2010)
Article
Biochemistry & Molecular Biology
Elaine M. Taylor, Nicola M. Bonsu, R. Jordan Price, Howard D. Lindsay
NUCLEIC ACIDS RESEARCH
(2013)
Article
Biochemistry & Molecular Biology
Ellaine M. Taylor, Alice C. Copsey, Jessica J. R. Hudson, Susanne Vidot, Alan R. Lehmann
MOLECULAR AND CELLULAR BIOLOGY
(2008)
Article
Cell Biology
S Yan, HD Lindsay, WM Michael
JOURNAL OF CELL BIOLOGY
(2006)