Article
Oncology
Nicola Lockwood, Silvia Martini, Ainara Lopez-Pardo, Katharina Deiss, Hendrika A. Segeren, Robert K. Semple, Ian Collins, Dimitra Repana, Mathias Cobbaut, Tanya Soliman, Francesca Ciccarelli, Peter J. Parker
Summary: G2 arrest is crucial for the faithful segregation of sister chromatids, and the p53-p21 signaling pathway plays an essential role in cell lines, patient-derived cells, and colorectal cancer organoids. In arrest-defective hTERT-positive cells, the PKC epsilon failsafe mechanism is engaged. In ALT-dependent cancer cells, a distinct form of p53-independent G2 arrest is mediated by BLM and Chk1.
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
Biochemical Research Methods
Himasha M. Perera, Michael A. Trakselis
Summary: Helicase enzymes play crucial roles in genome maintenance, and mutations in helicases are associated with various diseases. Previous studies have focused on the biochemical characterization and structural analysis of helicases, but the understanding of their active translocation orientations still requires the combination of structure and kinetics. This review explores different methods to map the binding orientations of helicases to DNA or RNA substrates and provides insights into defining the active leading and trailing faces of these enzymes.
Article
Biochemistry & Molecular Biology
Gijs Zonderland, Riccardo Vanzo, Sampath Amitash, Elena Martin-Doncel, Fabian Coscia, Andreas Mund, Mads Lerdrup, Jan Benada, Dominik Boos, Luis Toledo
Summary: In contrast to existing models, the TRESLIN-MTBP complex can prevent premature entry into G2 independently of ATR/CHK1 kinases in early S-phase. It acts as a monitoring system that checks the activation of replication forks and senses the rate of origin firing to prevent premature entry into G2.
Article
Multidisciplinary Sciences
Naining Xu, Qingpeng Lin, Honglei Tian, Changdong Liu, Peiyi Wang, Ching Monica Suen, Hongyu Yang, Ye Xiang, Guang Zhu
Summary: This study presents the cryo-EM structure of human MCM2-7 complex, revealing its capability to self-assemble into a loose double hexamer and suggesting a novel loading mechanism. The high-resolution cryo-EM structure of human MCM2-7 is critical for understanding the molecular mechanisms governing human DNA replication.
Article
Biochemistry & Molecular Biology
Martin Meagher, Alexander Myasnikov, Eric J. Enemark
Summary: The ATPase ring of the replication forks is essential for DNA replication and disruption of this ring can lead to genetic instability and diseases such as cancer. Using cryo-EM, researchers have found that the ATPase ring of the archaeal organism Saccharolobus solfataricus binds to the DNA in two different modes, revealing a mechanism for the alternating steps of DNA dissociation and re-association during DNA translocation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Oya Bermek, R. Scott Williams
Summary: HSV-1 is a herpesvirus that infects humans and encodes proteins for replicating its genome, including a helicase and primase. The helicase-primase complex of UL5/UL8/UL52 has three components, with UL5 and UL52 functionally interdependent and UL8 coordinating their activities. Antiviral compounds target the functions of UL5 and UL52 for potential alternative treatments.
Review
Biochemistry & Molecular Biology
Ilan Attali, Michael R. Botchan, James M. Berger
Summary: This article discusses recent progress in understanding the physical basis of replisome construction and progression in eukaryotes, highlighting the critical role played by large, dynamic protein-nucleic acid assemblies in this cellular process.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Article
Oncology
Stephanie Schaefer-Ramadan, Jovana Aleksic, Nayra M. Al-Thani, Joel A. Malek
Summary: This study used a next-generation sequencing-based protein-protein interaction method called AVA-Seq to identify protein contact points between TP53 and MCM complex proteins 2, 3, and 5. The interacting regions were determined with high resolution and novel domains were discovered. The findings provide a mini-network of known and novel cancer protein interactions, which could have implications for drug design and the effects of specific cancer mutations.
Review
Biochemistry & Molecular Biology
Emory G. Malone, Matthew D. Thompson, Alicia K. Byrd
Summary: Pif1 helicases are a multifunctional family of DNA helicases that play important roles in various cellular functions, including handling multiple barriers at the replication fork and regulating replication termination, fragment maturation, and break-induced replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Amy J. Fernandez, James M. Berger
Summary: Ring-shaped hexameric helicases are essential motor proteins that separate duplex nucleic acid strands for DNA replication, recombination, and transcriptional regulation. Two evolutionary distinct lineages based on RecA and AAA+ ATPase folds have been identified. Hexameric helicases couple NTP hydrolysis and conformational changes to move nucleic acid substrates.
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chen-Yu Lo, Yang Gao
Summary: Research suggests that T7 polymerase plays a dominant role in helicase-polymerase coupling and replisome progression. The helicase and polymerase sandwich the parental DNA, but only the polymerase carries the DNA with a positively charged cleft and stacks at the fork opening using a beta-hairpin loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Rachel A. Hoffman, Heather K. MacAlpine, David M. MacAlpine
Summary: This study provides insights into helicase activation within origin chromatin and its regulation in the absence of DNA replication. Activation of the helicase disrupts and disorganizes chromatin, extending up to 1 kb from early replication origins. The local sequence context plays a role in regulating helicase progression when uncoupled from replication.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Mary E. Anderson, Janet L. Smith, Alan D. Grossman
Summary: DNA replication is regulated primarily at the initiation step, where DnaA and oriC are the key targets. Multiple mechanisms including elongation and initiation can compensate for over-initiation, highlighting the complexity of replication regulation.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jiuyang Liu, Belen Chaves-Arquero, Pengcheng Wei, Adam H. Tencer, Antonio Ruiz-Albor, Gongyi Zhang, Francisco J. Blanco, Tatiana G. Kutateladze
Summary: FBH1 is involved in regulating cell responses to replicative stress and is recruited to stalled DNA replication forks by PCNA. It inhibits homologous recombination and catalyzes fork regression. This study reports the structural basis for the molecular recognition of two different motifs of FBH1 (FBH1PIP and FBH1APIM) by PCNA, revealing the overlapping binding sites of PCNA for FBH1PIP and FBH1APIM, with FBH1PIP making the dominant contribution to this interaction.
Article
Multidisciplinary Sciences
Tanu Rana, Olga Y. Korolkova, Girish Rachakonda, Amanda D. Williams, Alexander T. Hawkins, Samuel D. James, Amos M. Sakwe, Nian Hui, Li Wang, Chang Yu, Jeffrey S. Goodwin, Michael G. Izban, Regina S. Offodile, Mary K. Washington, Billy R. Ballard, Duane T. Smoot, Xuan-Zheng Shi, Digna S. Forbes, Anil Shanker, Amosy E. M'Koma
Summary: The study links bacterial enterotoxins and DEFA5 to the expansion of CCLCs in the colonic mucosa of Crohn's colitis (CC) patients. DEFA5 bioassay accurately discriminates between CC and ulcerative colitis (UC), showing a specific secretory role in the pathogenesis of CC.
Article
Biochemistry & Molecular Biology
Madhav Jagannathan, Yukiko M. Yamashita
Summary: The inefficient clustering of divergent satellite DNA in Drosophila hybrid cells leads to chromocenter disruption, micronuclei formation, and tissue atrophy, which is linked to the reproductive isolation between closely related species.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Review
Cell Biology
Franziska Brandle, Benjamin Fruhbauer, Madhav Jagannathan
Summary: In this paper, the literature on pericentromeric satellite DNA is reviewed and its organization and functions across eukaryotic species are discussed. The focus is on chromocenters, DNA-dense nuclear foci containing clustered pericentromeric satellite DNA repeats. The roles of epigenetic modifications, satellite DNA transcripts, and sequence-specific satellite DNA-binding in chromocenter formation are examined. Additionally, the emerging functions of chromocenters in genome encapsulation, maintaining cell fate, and speciation are reviewed, with an emphasis on the impact of rapid divergence of satellite DNA repeats on reproductive isolation between closely related species.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Stephen D. Williams, Amos M. Sakwe
Summary: The expression status of Annexin A6 (AnxA6) in TNBC cells determines the metabolic adaptations of basal-like and mesenchymal-like TNBC subsets, and has important implications for tumor growth, metastasis, and therapeutic resistance.
Meeting Abstract
Biochemistry & Molecular Biology
Stephen D. Williams, Amos M. Sakwe
Article
Endocrinology & Metabolism
Heather K. Beasley, Sarrah E. Widatalla, Diva S. Whalen, Stephen D. Williams, Olga Y. Korolkova, Clementine Namba, Siddharth Pratap, Josiah Ochieng, Amos M. Sakwe
Summary: The expression of MAGEC2 is induced by high Ca2+ levels and mediated by the AP-1 transcription factor in malignant TNBC tissues. The abnormal expression of MAGEC2 is associated with increased circulating Ca2+ levels.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell Biology
Stephen D. Williams, Tunde M. Smith, LaMonica Stewart, Amos M. Sakwe
Summary: Hypoxia in the tumor microenvironment affects the expression of Annexin A6 (AnxA6) in triple-negative breast cancer cells and their response to targeted therapies. Downregulation of AnxA6 inhibits resistance to EGFR and AR inhibitors, suggesting that targeting AnxA6 could be beneficial in overcoming drug resistance.
Editorial Material
Education, Scientific Disciplines
Jamaine S. Davis, Amos M. Sakwe, Aramandla Ramesh, Merry L. Lindsey, Letha Woods
Summary: We provide a framework for developing mentorship skills using the GREAT model, which includes giving opportunities and opening doors, helping students identify strengths and reach goals, serving as a positive example, advising as individuals, and training for independent thinking.
ADVANCES IN PHYSIOLOGY EDUCATION
(2023)
Article
Biochemistry & Molecular Biology
Carlos Virgous, Letitia Lyons, Amos Sakwe, Tultul Nayyar, Shawn Goodwin, James Hildreth, Kevin Osteen, Kaylon Bruner-Tran, Oluwatobi Alawode, Phillip Bourne, Edward Richard Hills, Anthony E. Archibong
Summary: Hydroxyurea (HU), a drug for cancer treatment and sickle cell anemia management, reduces male fertility. This study aimed to investigate the reversibility of HU-induced hypogonadism using adult male mice. After 2 months of HU treatment, fertility indices were significantly reduced. However, a 4-month withdrawal from HU resulted in improvements in fertility indices, including testis weight, sperm motility, and sperm density, as well as an increase in circulating testosterone level. Mating experiments showed that recovering males could produce viable offspring, qualifying HU as a potential male contraceptive.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Oncology
Stephen D. Williams, Sarrah E. Widatalla, Amos M. Sakwe
Meeting Abstract
Oncology
Stephen D. Williams, Sarrah E. Widatalla, Amos M. Sakwe
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Biochemistry & Molecular Biology
Josiah Ochieng, Olga Y. Korolkova, Guoliang Li, Renjie Jin, Zhenbang Chen, Robert J. Matusik, Samuel Adunyah, Amos M. Sakwe, Olugbemiga Ogunkua
Summary: The present studies evaluated key serum proteins and other components that mediate 3-D growth of LNCaP prostate cancer cells. It was found that fetuin-A is the serum protein that mediates this growth by sequestering extracellular vesicles on the surfaces of the cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Oncology
Stephen D. Williams, Sarrah E. Widatalla, Amos M. Sakwe
Meeting Abstract
Oncology
Heather K. Beasley, Ky'Era V. Actkins, Annika B. Faucon, Lea K. Davis, Amos M. Sakwe
Meeting Abstract
Biochemistry & Molecular Biology
Stephen Williams, Sarrah Widatalla, Amos Sakwe