Review
Genetics & Heredity
Yoshihisa Matsumoto, Anie Day D. C. Asa, Chaity Modak, Mikio Shimada
Summary: DNA-dependent protein kinase (DNA-PK) plays a key role in DNA damage repair and maintenance of genomic stability through its catalytic subunit (DNA-PKcs) and Ku70/Ku80 heterodimer. It acts as a sensor for DNA double-stranded breaks (DSB) and is essential for nonhomologous end joining (NHEJ) repair. Dysfunction in DNA-PKcs or Ku functions can lead to detrimental phenotypes, especially in neuronal and immune systems.
Article
Biochemistry & Molecular Biology
Ashley N. Chandra, Sayanthooran Saravanabavan, Gopala K. Rangan
Summary: DNA-PK may mediate kidney cyst growth in ADPKD through its effects on proliferation and survival, with the DNA-PK complex being overexpressed in human ADPKD and DNA-PKcs detected in the cyst lining epithelia. In vitro, DNA-PK kinase inhibitor NU7441 significantly reduced cyst growth and enhanced the anti-proliferative effects of sirolimus in ADPKD cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yuriko Sorimachi, Daiki Karigane, Yukako Ootomo, Hiroshi Kobayashi, Takayuki Morikawa, Kinya Otsu, Yoshiaki Kubota, Shinichiro Okamoto, Nobuhito Goda, Keiyo Takubo
Summary: The study revealed that p38 alpha plays a multi-modal role in HSC aging, regulating differentiation bias and transplantation capacity at different stages of chronological aging. Furthermore, codeletion of p38 alpha exacerbated aging-related HSC phenotypes in mice deficient in ataxia-telangiectasia mutated, showing the complex role of p38MAPK in both promoting and suppressing HSC aging.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Qianqian Xu, Peiyu Zhang, Xiaoyan Han, Huwei Ren, Weiyue Yu, Wei Hao, Bowen Luo, Muhammad Imran Khan, Ni Chen
Summary: This study investigates the pivotal role of Nuclear factor-erythroid 2-related factor 2 (NRF2) in the activation of DNA damage repair in lung cancer cells after x-rays exposure. The study shows that NRF2 knockdown disrupts damaged DNA repair and homologous recombination, and NRF2 activation mediates DNA damage response via the MAPK pathway. These findings suggest that NRF2 plays a critical role in the development of radioresistance, which is of great significance for the development of radiotherapies.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Cell Biology
Isadora Carolina Betim Pavan, Andressa Peres de Oliveira, Pedro Rafael Firmino Dias, Fernanda Luisa Basei, Luidy Kazuo Issayama, Camila de Castro Ferezin, Fernando Riback Silva, Ana Luisa Rodrigues de Oliveira, Livia Alves dos Reis Moura, Mariana Bonjiorno Martins, Fernando Moreira Simabuco, Joerg Kobarg
Summary: NEKs are a family of Ser/Thr protein kinases that play important roles in cell cycle, mitosis, DNA damage response, and other biological functions in vertebrate cells. Research has primarily focused on their involvement in mitosis regulation and cell cycle, but recent studies have also shown their participation in DNA damage response pathways.
Article
Cell Biology
Theresa Farhat, Amel Dudakovic, Jay H. Chung, Andre J. van Wijnen, Rene St-Arnaud
Summary: The catalytic subunit of DNA-PKcs plays a negative regulatory role in osteoblast differentiation, and inhibitors of DNA-PKcs may have therapeutic potential for bone regeneration and metabolic bone diseases.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biology
Christopher Warren, Nikola P. Pavletich
Summary: DNA double-strand breaks can have detrimental effects on cells, including mutations, chromosomal rearrangements, genome instability, and cancer. The kinase ATM plays a central role in sensing and responding to these breaks, however, the activation mechanism of ATM is not well understood. This study reveals the structure of human ATM and its complex with the Nbs1 FxF/Y motif, shedding light on the activation mechanism and its implications in DNA damage response.
Article
Biochemistry & Molecular Biology
Eunyoung Lee, Zhenan Liu, Nhu Nguyen, Angus C. Nairn, Audrey N. Chang
Summary: In this study, the researchers identified the main isoform of PP1c beta expressed in cardiac myocytes and investigated its role in maintaining RLC phosphorylation in vivo. They found that cardiac muscle pathogenesis in PP1c beta knockout animals involves upregulation of total PP1c alpha in myocytes and non-muscle cells. Additionally, they discovered that phosphorylated myofibrillar cardiac myosin is dephosphorylated by both myosin-targeted and soluble MYPT-independent PP1c beta activities. These findings enhance our understanding of cardiac-MLCP in vivo.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
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
Matthew Jessulat, Shahreen Amin, Mohsen Hooshyar, Ramy Malty, Mohamed Taha Moutaoufik, Mara Zilocchi, Zoe Istace, Sadhna Phanse, Hiroyuki Aoki, Katayoun Omidi, Daniel Burnside, Bahram Samanfar, Khaled A. Aly, Ashkan Golshani, Mohan Babu
Summary: The deletion of the yeast PKA catalytic subunit Tpk1 reduces NHEJ efficiency by phosphorylating Nej1 to influence repair protein recruitment and DNA resection. In mammalian cells, the PRKACB homolog also plays a similar role in NHEJ repair by phosphorylating XLF.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Joshua T. Burgess, Chee Man Cheong, Amila Suraweera, Thais Sobanski, Sam Beard, Keyur Dave, Maddison Rose, Didier Boucher, Laura Croft, Mark N. Adams, Kenneth O'Byrne, Derek J. Richard, Emma Bolderson
Summary: Banf1 plays a crucial role in DNA repair by modulating the activity of DNA-PKcs to control double-strand break repair pathway choice, thereby maintaining genome stability within the cell.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Isabel Weigand, Cristina L. Ronchi, Jens T. Vanselow, Kerstin Bathon, Kerstin Lenz, Sabine Herterich, Andreas Schlosser, Matthias Kroiss, Martin Fassnacht, Davide Calebiro, Silviu Sbiera
Summary: Mutations in the PRKACA gene are a common cause of cortisol-producing adrenocortical adenomas and Cushing's syndrome, affecting the binding of regulatory subunits and leading to reduced RII β protein levels. The study shows that phosphorylation of RII β at Ser(114) is necessary for its degradation, mediated by caspase 16, resulting in increased cortisol secretion in adrenocortical cells. These findings provide insight into the molecular mechanisms and pathophysiological relevance of R subunit degradation caused by PRKACA mutations in adrenal Cushing's syndrome.
Article
Biochemistry & Molecular Biology
Mateusz Kciuk, Adrianna Gieleci, Somdutt Mujwar, Mariusz Mojzych, Renata Kontek
Summary: The cyclin-dependent kinase (CDK) family plays a critical role in regulating transcription and cell-cycle progression. Recent studies have revealed their involvement in DNA damage response (DDR) and repair, impacting the fidelity of cell division and maintenance of genomic integrity.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Multidisciplinary Sciences
Adam H. Tencer, Jiuyang Liu, Jing Zhu, Nathaniel T. Burkholder, Yi Zhang, Wenwen Wu, Brian D. Strahl, Tomohiko Ohta, Tatiana G. Kutateladze
Summary: The ZZ domain of HERC2 recognizes a mimetic of the Nt-R cargo degradation signal, and the crystal structure of the DOC domain of HERC2 is reported. The study also reveals that autophagy stimulation promotes HERC2 targeting to the proteasome, indicating the role of HERC2 in the ubiquitin-dependent degradation pathways.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Venturina Stagni, Silvia Orecchia, Luca Mignini, Sara Beji, Ambra Antonioni, Cinzia Caggiano, Daniela Barila, Pamela Bielli, Claudio Sette
Summary: The interaction between the DNA damage response pathway and RNA metabolism is important in cancer. This study reveals that ATM kinase can phosphorylate RNA binding protein Sam68, regulating its function in the response to DNA damage. The findings uncover a new interaction between ATM and Sam68, providing insights into the functional interaction between the DDR pathway and RNA binding proteins.
