Article
Cell Biology
Jong-Hyuk Lee, Raghavendra A. Shamanna, Tomasz Kulikowicz, Nima Borhan Fakouri, Edward W. Kim, Louise S. Christiansen, Deborah L. Croteau, Vilhelm A. Bohr
Summary: Werner syndrome (WS) is an accelerated aging disorder characterized by genomic instability caused by WRN protein deficiency. The phosphorylation of WRN by CDK2 on serine residue 426 is critical for WRN to choose between non-homologous end joining (NHEJ) and homologous recombination (HR) pathways. The phosphorylation stabilizes WRN's affinity for RPA and enhances its role in long-range resection, a crucial step for HR.
Review
Biochemistry & Molecular Biology
Vincent E. Provasek, Joy Mitra, Vikas H. Malojirao, Muralidhar L. Hegde
Summary: The continuous process of DNA damage and repair is crucial for maintaining genomic integrity. Among different types of DNA damage, double-strand breaks (DSBs) are the most dangerous and require timely repair. DSB repair is particularly important for nondividing, post-mitotic cells in the central nervous system (CNS), as failure in these mechanisms can lead to disruptions in neural networks and motor functions. In addition to repair pathways, DNA damage response (DDR) signaling and hnRNP proteins have been found to play important roles in neuronal DSB repair and are linked to age-associated neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Huiming Lu, Anthony J. Davis
Summary: RecQ DNA helicases are a conserved protein family found in various organisms, playing important roles in cellular functions and potentially contributing to autosomal disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ioannis Emmanouilidis, Natalia Fili, Alexander W. Cook, Yukti Hari-Gupta, Alia dos Santos, Lin Wang, Marisa L. Martin-Fernandez, Peter J. I. Ellis, Christopher P. Toseland
Summary: Mammalian cells are constantly exposed to various DNA damaging events, leading to the activation of DNA repair pathways. Cas9-based genomic intervention allows for induced DSBs at defined quantities and locations across the human genome, utilizing custom-designed promiscuous guide RNAs based on in silico predictions. This provides a generic, low-cost, and rapid methodology for inducing controlled DNA damage in cell culture models.
Article
Oncology
Jiali Qin, Jie Fan, Gang Li, Shanting Liu, Zhensheng Liu, Yao Wu
Summary: The study found that radiation exposure may lead to mutations in DNA double-strand break repair genes, resulting in decreased DSB repair capacity and increased risk of PTMC.
CANCER CELL INTERNATIONAL
(2021)
Article
Cell Biology
Melanie Rall-Scharpf, Thomas W. P. Friedl, Shahar Biechonski, Michael Denkinger, Michael Milyavsky, Lisa Wiesmueller
Summary: The gender gap in DNA repair and its changes with aging have distinct effects on men and women.
Article
Geriatrics & Gerontology
Evrydiki Kravvariti, Panagiotis A. Ntouros, Nikolaos Vlachogiannis, Maria Pappa, Vassilis L. Souliotis, Petros P. Sfikakis
Summary: Defects in the DNA damage response and repair network accumulate during aging, leading to physical frailty. This study found that older individuals had increased levels of oxidative stress and DNA damage, as well as reduced DNA repair capacity, compared to younger controls. These abnormalities were more pronounced in frail older adults and were associated with individual frailty levels, suggesting their potential as biomarkers for frailty.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Review
Genetics & Heredity
Alice Libri, Timea Marton, Ludovic Deriano
Summary: DNA double-strand breaks are highly toxic and can be repaired via multiple DNA repair pathways. During V(D)J recombination, certain parameters restrict the repair of DSBs to the non-homologous end-joining pathway.
FRONTIERS IN GENETICS
(2022)
Article
Biology
Nadia Vertti-Quintero, Ethan Levien, Lucie Poggi, Ariel Amir, Guy-Franck Richard, Charles N. N. Baroud
Summary: This study demonstrates the use of microfluidic device to study DSBR at a single-cell level in yeast. The dynamics of DSBR were analyzed and a differential equation model was developed to obtain repair process rates. The study identified three types of DSB repair events that were previously unrecognized.
Review
Biochemistry & Molecular Biology
Ye -Rim Lee, Gi-Sue Kang, Taerim Oh, Hye-Ju Jo, Hye-Joon Park, G. -One Ahn
Summary: DNA-PKcs is a critical player in repairing DNA double-strand breaks and is involved in T and B cell development. Recent evidence suggests that DNA-PKcs not only functions in the nucleus but also in the cytoplasm, phosphorylating various proteins involved in cellular metabolism and cytokine production. Careful selection of experimental models is necessary when studying DNA-PKcs, as differences have been observed between cells with defective DNA-PKcs and cells with DNA-PKcs knockout. Additionally, the multiple functions and subcellular localization of DNA-PKcs in different cell types may complicate the effects of DNA-PK inhibitors in clinical trials.
MOLECULES AND CELLS
(2023)
Article
Cell Biology
Anke Geng, Shiya Xu, Yunxia Yao, Zhen Qian, Xiyue Wang, Jiahui Sun, Jingyuan Zhang, Fangfang Shi, Zhixi Chen, Weina Zhang, Zhiyong Mao, Wen Lu, Ying Jiang
Summary: Chrysin impairs genomic stability in breast cancer cells by inhibiting DNA double-strand break repair, which leads to accumulation of DNA damage and enhances sensitivity to chemotherapy. This compound also delays the recruitment of key factors involved in repair mechanisms, proposing a potential curative effect when combined with chemotherapy in breast cancer treatment.
Review
Biochemistry & Molecular Biology
Benjamin M. Stinson, Joseph J. Loparo
Summary: DNA double-strand breaks are mainly repaired through nonhomologous end joining (NHEJ) in vertebrates, which requires efficient end synapsis and processing mechanisms to maintain genome stability.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Article
Genetics & Heredity
Misaki Matsui, Shoki Kajita, Yuina Tsuchiya, Wakana Torii, Shiori Tamekuni, Ryotaro Nishi
Summary: Proper choice of DNA double-strand break (DSB) repair pathway is crucial for maintaining genome integrity. This study identifies USP49 as a novel enzyme that regulates ubiquitylation of DSB-induced gamma H2AX. Fine tuning of USP49 protein level and its deubiquitylation activity play important roles in cell sensitivity to DSB-inducing drug treatment.
Review
Cell Biology
Stephanie M. Ackerson, Carlan Romney, P. Logan Schuck, Jason A. Stewart
Summary: Regulation of DNA double-strand breaks and telomeres in cells is diametrically opposed, with DSBs requiring quick recognition and repair while telomeres must be protected to prevent unwanted chromosome fusions. Decision on whether to join DNA ends is critical for genome stability, and processing of telomeres and DSBs share commonalities. Repair of DSBs is determined by decision points that shift towards homologous recombination (HR) or non-homologous end joining (NHEJ).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Genetics & Heredity
Leonhard Andreas Karl, Martina Peritore, Lorenzo Galanti, Boris Pfander
Summary: DNA double strand breaks (DSBs) are repaired in eukaryotes by various cellular mechanisms. Nucleosome remodelers, which have the ability to slide, evict, position, or edit nucleosomes, have emerged as key regulators of DSB repair. The activities of nucleosome remodelers at DSBs have been found to impact the decision-making process of DSB repair.
FRONTIERS IN GENETICS
(2022)
Article
Biotechnology & Applied Microbiology
C. F. M. Menck, R. S. Galhardo, A. Quinet
Summary: Studies have shown that xeroderma pigmentosum variant (XP-V) patients have mutations in the POLH gene, resulting in a high frequency of skin tumors. However, it is paradoxical that the translesion synthesis DNA polymerase eta (Pol η) in these patients can actually suppress mutations, and the mechanism behind this is still unclear. Recent evidence suggests that cyclobutane pyrimidine dimers (CPDs) play an instructional role for Pol η, enabling accurate replication of these lesions, and the mutagenic effects induced by UV radiation are caused by the deamination of C-containing CPDs. This process leads to C>T transitions, which are the most common mutations in skin cancers. The delayed replication in XP-V cells amplifies the deamination of C in CPDs and increases the burden of C>T mutations through the activity of backup TLS polymerases.
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2024)