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)
Article
Biochemistry & Molecular Biology
Arvind Panday, Nicholas A. Willis, Rajula Elango, Francesca Menghi, Erin E. Duffey, Edison T. Liu, Ralph Scully
Summary: The study reveals that the FANCM gene encodes a multi-domain scaffolding and motor protein that regulates repair pathway choice at stalled replication forks, and its ATPase function may be a promising target for therapy of BRCA1-linked cancer.
Article
Biochemistry & Molecular Biology
Archana Krishnamoorthy, Jessica Jackson, Taha Mohamed, Madison Adolph, Alessandro Vindigni, David Cortez
Summary: RAD51 facilitates replication fork reversal and RADX can either inhibit or promote fork reversal depending on replication stress levels. RADX interacts directly with RAD51 and single-strand DNA to confine fork reversal to persistently stalled forks, preventing genome instability.
Article
Biochemistry & Molecular Biology
Debolina Bandyopadhyay, Padmaja Prasad Mishra
Summary: This study investigates the helicase activity mechanism of RecG and reveals its enhanced processivity for stalled forks. RecG catalyzes the formation of Holliday junction and adopts an asymmetric mode of locomotion to unwind the lagging daughter strand.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jonathan Heuze, Samira Kemiha, Antoine Barthe, Alba Toran Vilarrubias, Elyes Aouadi, Umberto Aiello, Domenico Libri, Yea-Lih Lin, Armelle Lengronne, Jerome Poli, Philippe Pasero
Summary: R-loops, RNA:DNA hybrids, act as barriers to replication forks and interfere with postreplicative fork repair mechanisms if not promptly degraded by RNase H. Cells lacking RNase H exhibit impaired replication under challenging conditions, and triptolide, an inhibitor of transcription, restores fork resection.
Article
Biochemistry & Molecular Biology
Swagata Halder, Lepakshi Ranjha, Angelo Taglialatela, Alberto Ciccia, Petr Cejka
Summary: SMARCAL1, ZRANB3 and HLTF are important factors in remodeling replication forks to maintain genome stability. RAD51 and the RAD51 paralog complex have recombination-independent functions in fork reversal, possibly through physical interactions with SMARCAL1 and ZRANB3.
NUCLEIC ACIDS RESEARCH
(2022)
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)
Article
Multidisciplinary Sciences
Yang Liu, Lu Wang, Xin Xu, Yue Yuan, Bo Zhang, Zeyang Li, Yuchen Xie, Rui Yan, Zeqi Zheng, Jianguo Ji, Johanne M. Murray, Antony M. Carr, Daochun Kong
Summary: This study reveals the mechanism by which the checkpoint kinases Rad3ATR and Cds1Chk2 directly regulate the replicative helicase under replication stress. When replication forks stall, Cds1Chk2 phosphorylates Cdc45, reducing CMG helicase activity and preserving the integrity of stalled replisomes and replication forks.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Steven J. Sandler, Maxime Leroux, Tricia A. Windgassen, James L. Keck
Summary: This study investigates two biochemical and genetic mechanisms of the PriA-PriB pathway in Escherichia coli, one utilizing PriB-stimulated helicase activity to release a region of ssDNA and the other involving helicase-independent remodeling activity.
MOLECULAR MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Piero R. Bianco
Summary: The rescue of stalled DNA replication forks is crucial for cell viability. Both the bacterial helicase RecG and the eukaryotic enzyme SMARCAL1 can regress forks, but there are key differences between them, including their directionality and processivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Morgan L. Jones, Yasemin Baris, Martin R. G. Taylor, Joseph T. P. Yeeles
Summary: This study determined the structure of a human replisome containing multiple proteins, revealing their interactions and providing insights into the working mechanism of the replisome and how it maintains smooth replication progression.
Article
Genetics & Heredity
Julius Muellner, Kristina H. Schmidt
Summary: To ensure genome stability, replication progress needs to be monitored and accurately completed. In the yeast Saccharomyces cerevisiae, the DNA helicase Rrm3, belonging to the PIF1 family, facilitates replication fork progression through an unknown mechanism. Disrupting Rrm3 helicase activity leads to increased replication fork pausing in the yeast genome.
Article
Microbiology
Lindsay A. Matthews, Lyle A. Simmons
Summary: PriA is a crucial protein found in almost all bacteria that recognizes stalled replication forks and aids in their restart. This study focused on analyzing the importance of the winged helix (WH) domain and an associated linker in Bacillus subtilis (B. subtilis). The results showed that both the WH domain and linker are critical for surviving DNA damage in B. subtilis, and they may play different roles in diverse bacterial organisms.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Oncology
Nicholas J. Panzarino, John J. Krais, Ke Cong, Min Peng, Michelle Mosqueda, Sumeet U. Nayak, Samuel M. Bond, Jennifer A. Calvo, Mihir B. Doshi, Matt Bere, Jianhong Ou, Bin Deng, Lihua J. Zhu, Neil Johnson, Sharon B. Cantor
Summary: The sensitivity of BRCA-deficient cancers is attributed to the presence of ssDNA replication gaps, rather than defects in homologous recombination or fork protection. The restoration of fork restraint or gap filling can confer therapy resistance, while restored FP and HR do not necessarily contribute to therapy resistance in the presence of gaps. Additionally, the study suggests that DNA double-strand breaks are induced from cell death nucleases and are not fundamental to the mechanism of action of genotoxic agents.
Article
Cell Biology
Arik Townsend, Gabriella Lora, Justin Engel, Neysha Tirado-Class, Huzefa Dungrawala
Summary: DCAF14, a substrate receptor for the CRL4 complex, plays a crucial role in stabilizing stalled replication forks and preventing double-strand breaks, thereby promoting genome integrity. This study demonstrates the replication stress response functions of DCAF14 in ensuring genome maintenance.
Article
Biochemistry & Molecular Biology
Andrew C. Kile, Diana A. Chavez, Julien Bacal, Sherif Eldirany, Dmitry M. Korzhnev, Irina Bezsonova, Brandt F. Eichman, Karlene A. Cimprich
Article
Biochemistry & Molecular Biology
Elwood A. Mullins, Rongxin Shi, Brandt F. Eichman
NATURE CHEMICAL BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Garrett M. Warren, Richard A. Stein, Hassane S. Mchaourab, Brandt F. Eichman
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2018)
Article
Biochemistry & Molecular Biology
Jacob L. Steenwyk, Dana A. Opulente, Jacek Kominek, Xing-Xing Shen, Xiaofan Zhou, Abigail L. Labella, Noah P. Bradley, Brandt F. Eichman, Neza Cadez, Diego Libkind, Jeremy DeVirgilio, Amanda Beth Hulfachor, Cletus P. Kurtzman, Chris Todd Hittinger, Antonis Rokas
Article
Biochemistry & Molecular Biology
Petria S. Thompson, Katherine M. Amidon, Kareem N. Mohni, David Cortez, Brandt F. Eichman
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2019)
Article
Genetics & Heredity
Maryam Imani Nejad, Kurt Housh, Alyssa A. Rodriguez, Tuhin Haldar, Scott Kathe, Susan S. Wallace, Brandt F. Eichman, Kent S. Gates
Article
Biochemistry & Molecular Biology
Alyssa A. Rodriguez, Jessica L. Wojtaszek, Briana H. Greer, Tuhin Haldar, Kent S. Gates, R. Scott Williams, Brandt F. Eichman
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Xiaorong Chen, Noah P. Bradley, Wei Lu, Katherine L. Wahl, Mei Zhang, Hua Yuan, Xian-Feng Hou, Brandt F. Eichman, Gong-Li Tang
Summary: This study identifies four DNA glycosylases important for the biosynthesis of aromatic polyketide antibiotics, which provide self-resistance to producing strains by removing intercalated guanine adducts. These enzymes are highly specific for the antibiotic-DNA lesions and have no activity toward other alkylguanines. Moreover, abasic sites generated from one of the DNA glycosylases are less efficiently repaired compared to other types of DNA damage.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Elwood A. Mullins, Jonathan Dorival, Gong-Li Tang, Dale L. Boger, Brandt F. Eichman
Summary: Microbial DNA glycosylases associated with DNA-damaging antibiotics have evolved self-resistance through reduced product affinity, rather than enhanced substrate recognition, indicating an evolutionary outcome of selective pressure for self-protection against certain natural products.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Noah P. Bradley, Katherine L. Wahl, Jacob L. Steenwyk, Antonis Rokas, Brandt F. Eichman
Summary: Bacteria are rich sources of secondary metabolites with DNA-damaging properties, including genotoxins with antitumor/antibiotic properties. However, targeted discovery of biosynthetic gene clusters (BGCs) producing DNA-damaging agents from Streptomyces is lacking. This study identified two families of DNA repair enzymes, one specific for complex alkyl-DNA lesions and involved in self-resistance to antimicrobials, and the other likely involved in protection against an array of genotoxins. This work provides a framework for targeted discovery of new genotoxic compounds with therapeutic potential.
Article
Biochemistry & Molecular Biology
Jonathan Dorival, Brandt F. Eichman
Summary: This study reveals the nuclease activities of human TatD paralogs TATDN1 and TATDN3, which include both 3'-5' exonuclease activity and AP endonuclease activity. The two nuclease activities are exhibited in different types of DNA and are regulated by divalent metal cofactors. The study also shows that the three E. coli TatD paralogs also possess AP endonuclease activity.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Brandt F. Eichman
Summary: The replication machinery frequently encounters obstacles that hinder the replication fork. Replication-coupled processes that remove or bypass these barriers are crucial for replication completion and genome stability. Errors in replication-repair pathways lead to genetic mutations and human diseases.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Noah Bradley, Katherine Wahl, Jacob Steenwyk, Plamen Christov, Lauren Washburn, Coran Watanabe, Antonis Rokas, Brandt Eichman
Article
Biochemistry & Molecular Biology
Rongxin Shi, Elwood A. Mullins, Xing-Xing Shen, Kori T. Lay, Philip K. Yuen, Sheila S. David, Antonis Rokas, Brandt F. Eichman