Article
Biochemistry & Molecular Biology
Katarzyna H. Maslowska, Florencia Villafanez, Luisa Laureti, Shigenori Iwai, Vincent Pages
Summary: This study reveals that Translesion Synthesis (TLS) is locally controlled by PCNA ubiquitination at each individual lesion after a genotoxic stress. Activation of the DDR does not promote TLS and mutagenesis, in contrast to the SOS response in bacteria.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Fengwei Zheng, Roxana Georgescu, Nina Y. Yao, Huilin Li, Michael E. O'Donnell
Summary: The RFC complex has been shown to have a second DNA binding site, located between the N-terminal BRCT domain and AAA+ module of the large Rfc1 subunit. This 5' DNA site exhibits ideal binding to a 7-nt gap and shows enhanced binding to 5 and 10 nt gaps. It is proposed that the 5' site facilitates RFC's PCNA loading activity at DNA damage-induced gaps and plays a potential role in lagging strand DNA synthesis.
Review
Biochemistry & Molecular Biology
Giulio Ticli, Ornella Cazzalini, Lucia A. Stivala, Ennio Prosperi
Summary: The p21(CDKN1A) protein is involved in maintaining genome stability by inhibiting DNA synthesis, interacting with DNA damage response proteins, and regulating the efficiency of DNA replication and repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Hyun Ji Hwang, Seong Hwi Hong, Hong Sang Moon, Young Eun Yoon, Sung Yul Park
Summary: This study found that the combination therapy of ginsenoside and sunitinib significantly enhances the inhibition of cell viability in clear cell renal cell carcinoma (ccRCC) cells, and inhibits cell proliferation by inducing oxidative DNA damage.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Shaked Nir Heyman, Mika Golan, Batia Liefshitz, Martin Kupiec
Summary: PCNA acts as a processivity factor and a landing pad for proteins during DNA synthesis. The interaction between PCNA and Pol delta is mediated by PIPs, specifically on Pol32. The weak interaction of the exonuclease mutant pol3-01 with PCNA leads to increased mutagenesis and sister chromatid recombination.
Article
Medicine, Research & Experimental
Masoumeh Moradi-Ozarlou, Sana Moshari, Hamed Rezaei Agdam, Amir Nomanzadeh, Simineh Shahmohamadlou, Mazdak Razi
Summary: The study found that obese rats induced by HFD showed a significant increase in mRNA levels of Hsp70-2a and Hsp90, while the mRNA levels of PCNA and the percentage of PCNA+ cells were decreased in the obese group. Additionally, obesity led to a significant decrease in testicular TAC, resulting in a reduction in serum testosterone levels, along with cell DNA and RNA damage.
Article
Biology
Marina Schrecker, Juan C. Castaneda, Sujan Devbhandari, Charanya Kumar, Dirk Remus, Richard K. Hite
Summary: The research discovered that PCNA can adopt both open and closed conformations in the RFC:PCNA:DNA complex, allowing for direct insertion of dsDNA. Additionally, the study revealed that the RFC-catalyzed loading of PCNA onto DNA involves multiple steps, with partial melting facilitating lateral insertion into the central RFC:PCNA channel.
Article
Plant Sciences
Martina Nespor Dadejova, Michal Franek, Martina Dvorackova
Summary: This study presents a method for studying the DNA damage response in plants using plant protoplasts. DNA lesions were generated using laser microirradiation, and fluorescently tagged proteins were introduced to study the localization and function of uncharacterized plant proteins in the protoplasts. The results demonstrate that laser microirradiation in protoplasts induces a physiological cellular response and recruits factors involved in DNA repair.
Article
Cell Biology
Cristina Gonzalez-Garrido, Felix Prado
Summary: The advance and stability of replication forks are regulated by the coordination of DNA synthesis and nucleosome assembly. Mutants with impaired parental histone recycling exhibit defects in recombinational repair of single-stranded DNA gaps generated during replication. These defects are caused by excessive parental nucleosomes at the invaded strand and interference with strand invasion via a Srs2-dependent mechanism. Additionally, the location of replication obstacles and distribution of parental histones regulate homologous recombination, with hindrance on the lagging strand showing greater sensitivity.
Article
Biochemistry & Molecular Biology
Jun Che, Xin Hong, Hai Rao
Summary: Lesions in DNA that escape repair can block DNA replication, which is handled during the S/G2 phases by damage tolerance mechanisms such as TLS and TS. The ubiquitylation of PCNA plays a critical role in determining the choice between TLS and TS pathways, with competition between the two pathways being influenced by the type of DNA lesion.
Article
Engineering, Biomedical
Eunseo Choi, Madeleine Landry, Nathan Pennock, Megan Neufeld, Katherine Weinfurter, Andrea Goforth, Joshua Walker, Conroy Sun
Summary: Recent studies have shown that combination radiotherapy and immunotherapy can improve outcomes. This study explores the use of folate-modified hafnium-based metal-organic frameworks as enhancers for radiotherapy and immune activation. The combination of HfMOF-PEG-FA with imiquimod effectively stimulates the immune response and enhances the antitumor effects of radiotherapy.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Genetics & Heredity
James P. Wells, Emily Yun-Chia Chang, Leticia Dinatto, Justin White, Stephanie Ryall, Peter C. Stirling
Summary: DNA replication is a vulnerable time for genome stability maintenance. This study reveals that RAD18 plays a crucial role in coordinating DNA damage tolerance pathways, preventing transcription-replication conflicts, and stabilizing DNA:RNA hybrids during replication. Failure to recruit FANCD2 protein at difficult to replicate and R-loop prone sites leads to increased transcription-replication conflicts and DNA double strand breaks.
Review
Microbiology
Matan Arbel, Batia Liefshitz, Martin Kupiec
Summary: The origin of mutations is not random, but largely caused by genetically encoded error-prone repair mechanisms. Cells are still unclear about when to use which repair method. For the yeast Saccharomyces cerevisiae, at least two error-free and two error-prone inter-related mechanisms of damage tolerance have been identified.
FEMS MICROBIOLOGY REVIEWS
(2021)
Review
Genetics & Heredity
Michelle Shen, Adrian Young, Chantal Autexier
Summary: The maintenance of telomeres is crucial for the immortalization of cancer cells, with approximately 10-15% of cancer cells utilizing the ALT pathway to maintain their telomeres. Telomeres pose a challenge to DNA replication due to their repetitive nature and potential for forming secondary structures, especially in ALT(+) cells with elevated replication stress levels. Various DNA metabolic strategies exist to counter replication stress, with PCNA playing a key role in recruiting protein partners for DNA replication and repair pathways. Analysis of PCNA and its post-translational modifications may provide insight into the unique DNA metabolic landscape at ALT(+) telomeres.
Editorial Material
Biochemistry & Molecular Biology
David Jeruzalmi
Summary: Eukaryotes possess various clamp loaders, each with four common subunits and a unique fifth subunit. The RFC-A-E clamp loader loads the PCNA clamp at 3'-recessed DNA structures, while swapping the Rad24 subunit for RFC-A results in a loader that prefers the 911 clamp and 5'-recessed DNA. Recent studies provide detailed insights into the clamp loading reaction and substrate preferences of each loader.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Christian Renz, Veronique Albanese, Vera Troester, Thomas K. Albert, Olivier Santt, Susan C. Jacobs, Anton Khmelinskii, Sebastien Leon, Helle D. Ulrich
JOURNAL OF CELL SCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Nicola Zilio, Helle D. Ulrich
Summary: Mapping the genome-wide distribution of single-strand breaks is crucial for understanding damage signaling and DNA repair. This article reviews classical and newly developed high-resolution methods for mapping single-strand breaks, highlighting the valuable insights they provide into the impact of this type of damage on the genome.
Article
Biochemistry & Molecular Biology
Vaclav Brazda, Yu Luo, Martin Bartas, Patrik Kaura, Otilia Porubiakova, Jiri Stastny, Petr Pecinka, Daniela Verga, Violette Da Cunha, Tomio S. Takahashi, Patrick Forterre, Hannu Myllykallio, Miroslav Fojta, Jean-Louis Mergny
Article
Biochemistry & Molecular Biology
Maria Cano-Linares, Aurora Yanez-Vilches, Nestor Garcia-Rodriguez, Marta Barrientos-Moreno, Roman Gonzalez-Prieto, Pedro San-Segundo, Helle D. Ulrich, Felix Prado
Summary: This study reveals that the HR protein Rad52 works in conjunction with the TLS machinery to repair MMS and UV light-induced ssDNA gaps. Rad52 facilitates DNA damage-induced mutagenesis and PCNA ubiquitylation through Rad51/Rad57-dependent and -independent processes, providing a novel role for recombination proteins in maintaining genome integrity.
Article
Genetics & Heredity
Ronald P. Wong, Kirill Petriukov, Helle D. Ulrich
Summary: Dealing with DNA lesions during genome replication is challenging, but repairing daughter-strand gaps through translesion synthesis or recombination-mediated template switching is crucial for genome maintenance. Proper control over the activities of daughter-strand gaps has important implications for cancer therapy.
Article
Multidisciplinary Sciences
Diane T. Takahashi, Daniele Gadelle, Keli Agama, Evgeny Kiselev, Hongliang Zhang, Emilie Yab, Stephanie Petrella, Patrick Forterre, Yves Pommier, Claudine Mayer
Summary: In this study, the structure of archaeal CsTOP1 in the absence of DNA was solved, revealing an open conformation resulting from a rotation between the CAP and CAT modules. The flexibility of the hinge, a five-residue loop connecting these modules, allows the opening/closing of the enzyme and the entry of DNA. A conserved tyrosine near the hinge was identified as mediating the transition from the open to closed conformation upon DNA binding.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Sabrina Wegmann, Cindy Meister, Christian Renz, George Yakoub, Hans-Peter Wollscheid, Diane T. Takahashi, Ivan Mikicic, Petra Beli, Helle D. Ulrich
Summary: This study presents a strategy for reprogramming the linkage of polyubiquitin chains using tailor-made ubiquitin ligases, and demonstrates that altering the features of a polyubiquitin chain can change the fate of the modified substrate, using the budding yeast replication factor PCNA as a model case. The study also provides evidence for redundancy between structurally similar linkages and shows that the method can be generalized to targets beyond PCNA.
Editorial Material
Biochemistry & Molecular Biology
David R. Corey, Helle D. Ulrich
NUCLEIC ACIDS RESEARCH
(2022)
Article
Genetics & Heredity
Hans-Peter Wollscheid, Helle D. Ulrich
Summary: The actin cytoskeleton is crucial for cellular processes in the nucleus, particularly in genome maintenance. Recent studies have found that nuclear F-actin plays important roles in DNA damage and replication stress responses, regulating intra-nuclear mobility and nuclear shape maintenance.
Article
Multidisciplinary Sciences
George Yakoub, Yun-Seok Choi, Ronald P. Wong, Tina Strauch, Kezia J. Ann, Robert E. Cohen, Helle D. Ulrich
Summary: This study describes the design and application of avidity-based probes against the ubiquitylated forms of PCNA in budding yeast. These probes can be tuned to regulate PCNA ubiquitylation and can be used as biosensors or inhibitors. In live cells, they reveal the timing and site-specific sensitivity of PCNA ubiquitylation.
Article
Genetics & Heredity
Tomio S. Takahashi, Violette Da Cunha, Mart Krupovic, Claudine Mayer, Patrick Forterre, Daniele Gadelle
NAR GENOMICS AND BIOINFORMATICS
(2020)