Article
Biochemistry & Molecular Biology
Alison C. Carley, Manisha Jalan, Shyamal Subramanyam, Rohini Roy, Gloria E. O. Borgstahl, Simon N. Powell
Summary: Loss of RAD52 in BRCA-deficient cells is synthetically lethal due to its role in backup homologous recombination repair. We demonstrate that phosphorylation of RPA is necessary for RAD52 to function as a mediator in HR, especially in BRCA-deficient cells.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
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.
Article
Cell Biology
Vera Chesnokova, Svetlana Zonis, Athanasia Apostolou, Hannah Q. Estrada, Simon Knott, Kolja Wawrowsky, Kathrin Michelsen, Anat Ben-Shlomo, Robert Barrett, Vera Gorbunova, Katia Karalis, Shlomo Melmed, Kolja Wawrowsky, Kathrin Michelsen, Anat Ben-Shlomo, Robert Barrett, Vera Gorbunova, Katia Karalis, Shlomo Melmed
Summary: The study found that as individuals age, the level of non-pituitary growth hormone (npGH) in the body increases, leading to DNA damage accumulation. npGH can suppress p53 and weaken DNA repair response, accelerating DNA damage. Inhibiting npGH signaling could be a potential anti-aging therapy strategy.
Article
Biochemistry & Molecular Biology
Ryo Sakasai, Tadashi Matsui, Yumi Sunatani, Kuniyoshi Iwabuchi
Summary: Camptothecin (CPT) shows cytotoxicity by inducing DNA double-strand breaks (DSBs) in DNA replication. The CPT-induced DSBs are considered to have only one DNA end, unlike radiation-induced DSBs that have two DNA ends. The cellular responses to one-ended and two-ended DSBs are not well understood.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Dominic Bazzano, Stephanie Lomonacol, Thomas E. Wilson
Summary: This study monitored the resection of the 5'-terminated strand at DNA double-strand breaks (DSBs) using high-throughput sequencing with molecular identifiers, revealing the roles of enzymes such as Mre11 and Exo1 in the process. Results showed a major Mre11-dependent cleavage position 60-70 bp from the DSB end and an Exo1-dependent pause point approximately 200 bp from the DSB.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Genetics & Heredity
Michelle L. Swift, Kate Beishline, Jane Azizkhan-Clifford
Summary: This study demonstrates the importance of Sp1 phosphorylation by ATM in facilitating the interaction with p300 for DSB repair. The recruitment of p300 to DSBs by Sp1 is essential for modifying histones and recruiting repair factors. Depletion of Sp1 leads to defects in histone acetylation and recruitment of repair proteins, highlighting the critical role of Sp1 in regulating chromatin remodelers for proper DSB repair.
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)
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
Genetics & Heredity
Atsushi Shibata, Penny A. Jeggo
Summary: ATM is a central kinase that activates a wide range of responses to cellular stress through signaling. It plays multiple roles in response to DNA damage, particularly focusing on DSB repair. Dysfunction in stress responses impairs repair accuracy, leading to dramatic sensitivity to ionizing radiation in ataxia telangiectasia (A-T) cells.
Article
Cell Biology
You-hong Wang, Zhen Guo, Liang An, Yong Zhou, Heng Xu, Jing Xiong, Zhao-qian Liu, Xiao-ping Chen, Hong-hao Zhou, Xiong Li, Tao Liu, Wei-hua Huang, Wei Zhang
Summary: This study found that LINC-PINT is significantly downregulated in nasopharyngeal cancer tissues compared to rhinitis tissues, and low LINC-PINT expressions are associated with poorer prognosis in patients receiving radiotherapy. LINC-PINT plays a functional role in inhibiting malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT inhibits DNA damage repair through the ATM/ATR-Chk1/Chk2 signaling pathways and increases radiosensitivity by interacting with DNA-PKcs.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Foon Wu-Baer, Madeline Wong, Lydia Tschoe, Chyuan-Sheng Lin, Wenxia Jiang, Shan Zha, Richard Baer
Summary: Homology-directed repair (HDR) of double-strand DNA breaks (DSBs) relies on the enzymatic resection of DNA ends by CtIP/Sae2 protein, with ATM/ATR phosphorylation enhancing DNA resection but not essential for animal development.
Article
Biochemistry & Molecular Biology
Rachel Bayley, Valerie Borel, Rhiannon J. Moss, Ellie Sweatman, Philip Ruis, Alice Ormrod, Amalia Goula, Rachel M. A. Mottram, Tyler Stanage, Graeme Hewitt, Marco Saponaro, Grant S. Stewart, Simon J. Boulton, Martin R. Higgs
Summary: The study suggests that methylation of histone H3 by SETD1A-BOD1L contributes to the recruitment of RIF1 to double-strand breaks, preventing excessive degradation of DNA ends and maintaining genome stability. This mechanism plays a crucial role in preserving telomere function and class switch recombination, and may be associated with the treatment and resistance of certain cancers.
Article
Cell Biology
Michelle L. Swift, Kate Beishline, Samuel Flashner, Jane Azizkhan-Clifford
Summary: This passage discusses the role of Sp1 in the cell cycle and its regulation of DSB repair pathway choice, favoring NHEJ repair. Sp1 is shown to recruit the NHEJ repair factor 53BP1 in G1 phase, while being evicted through phosphorylation in S phase, inhibiting HR repair.
Review
Biochemistry & Molecular Biology
Matvey Mikhailovich Murashko, Ekaterina Mikhailovna Stasevich, Anton Markovich Schwartz, Dmitriy Vladimirovich Kuprash, Aksinya Nicolaevna Uvarova, Denis Eriksonovich Demin
Summary: Incorrect repair of DNA double-strand breaks leading to chromosomal rearrangements is a major cause of oncogenesis. Recent studies have highlighted the key role of various types of RNA in the formation, recognition, and repair of DSBs, with gene mutations or changes in RNA expression levels potentially leading to DNA repair defects and increased chromosome aberration frequency. Additionally, certain RNAs have been shown to stimulate long-range chromosomal rearrangements, and further research is needed to understand how RNA mediates specific chromosomal rearrangements.
Review
Genetics & Heredity
Gerarda van de Kamp, Tim Heemskerk, Roland Kanaar, Jeroen Essers
Summary: Particle radiation, with its superior dose distribution compared to photon radiation, shows promise for tumor treatment. However, the cellular responses, particularly the DNA damage response (DDR), to particle therapy are not well characterized. Current investigations are focused on how the spatial configuration of DNA damage induced by particles influences DNA repair pathway usage.
FRONTIERS IN GENETICS
(2021)