Explanipedia

Depletion of BRD9-mediated R-loop accumulation inhibits leukemia cell growth via transcription–replication conflict Open

Seo Yun Lee, Soo Hyun Lee, M. Kwak, Ja Young Kim, Jullian Perren , et al. · 2025

Bromodomain-containing protein 9 (BRD9) has emerged as a promising therapeutic target for blood cancers, including acute myeloid leukemia, acute lymphoblastic leukemia, and multiple myeloma. PROTAC-based BRD9 degraders effectively hamper t…

MePCE promotes homologous recombination through coordinating R-loop resolution at DNA double-stranded breaks Open

Sravan K. Devanathan, Yi-Ru Li, Samantha B. Shelton, Jennifer M. K. Nguyen, Wei-Che Tseng , et al. · 2025

MePCE is a multifunctional protein that regulates the positive transcription elongation factor b (P-TEFb) partitioning between the nucleosol and chromatin. MePCE's role in sequestering P-TEFb in the nucleosol via the 7SK ribonuclear protei…

Abstract 1962 Role of histone N-terminal acetylation in genome integrity Open

Antonis Kirmizis, Ariel Klavaris, Cem Özdemir, Andrey Tvardovskiy, Till Siebenmorgen , et al. · 2025

Tracing Cellular Senescence in Bone: Time‐Dependent Changes in Osteocyte Cytoskeleton Mechanics and Morphology Open

Maryam Tilton, Junhan Liao, Chanul Kim, Hossein Shaygani, Maria Astudillo Potes , et al. · 2025

Aging‐related bone loss significantly impacts the growing elderly population globally, leading to debilitating conditions such as osteoporosis. Senescent osteocytes play a crucial role in the aging process of bone. This longitudinal study …

Identification of modulators of the ALT pathway through a native FISH-based optical screen Open

Benura Azeroglu, Shikhar Khurana, Shih-Chun Wang, Gianna M. Tricola, Shalu Sharma , et al. · 2024

A significant portion of human cancers utilize a recombination-based pathway, alternative lengthening of telomeres (ALT), to extend telomeres. To gain further insights into this pathway, we developed a high-throughput imaging-based screen …

Identification of Novel Modulators of the ALT Pathway Through a Native FISH-Based Optical Screen Open

Benura Azeroglu, Shikhar Khurana, Shih-Chun Wang, Gianna M. Tricola, Shalu Sharma , et al. · 2024

Summary A significant portion of human cancers utilize a recombination-based pathway, Alternative Lengthening of Telomeres (ALT), to extend telomeres. To gain further insights into this pathway, we developed a high-throughput imaging-based…

TRIM24 directs replicative stress responses to maintain ALT telomeres via chromatin signaling Open

Daein Kim, Ragini Bhargava, Shih-Chun Wang, Doo‐Hyung Lee, Riya Patel , et al. · 2024

An inability to replicate the genome can cause replication stress and genome instability. Here, we develop BLOCK-ID, a proteomic method to identify and visualize proteins at stressed replication forks. This approach successfully identified…

RPS19 and RPL5, the most commonly mutated genes in Diamond Blackfan anemia, impact DNA double-strand break repair Open

Nicholas F. DeCleene, Elif Aşık, Anthony Sanchez, Christopher L. Williams, Elena B. Kabotyanski , et al. · 2024

Diamond Blackfan anemia (DBA) is caused by germline heterozygous loss-of-function pathogenic variants (PVs) in ribosomal protein (RP) genes, most commonly RPS19 and RPL5 . In addition to red cell aplasia, individuals with DBA are at increa…

DOT1L: orchestrating methylation-dependent radiotheRAPy responses via BRCA1 Open

Justin Leung, Kyle M. Miller · 2024

Epitranscriptome in action: RNA modifications in the DNA damage response Open

Blerta Xhemalçe, Kyle M. Miller, Natalia Gromak · 2024

Biochemical Characterisation of the Short Isoform of Histone N-Terminal Acetyltransferase NAA40 Open

Ariel Klavaris, Maria Kouma, Cem Özdemir, Vicky Nicolaidou, Kyle M. Miller , et al. · 2024

N-alpha-acetyltransferase 40 (NAA40) is an evolutionarily conserved N-terminal acetyltransferase (NAT) linked to oncogenesis and chemoresistance. A recent study reported the generation of a second, shorter NAA40 isoform (NAA40S) through al…

PCAF promotes R-loop resolution via histone acetylation Open

Seo Yun Lee, Soo Hyun Lee, Nak Hun Choi, Ja Young Kim, Jun Hee Kweon , et al. · 2024

R-loops cause genome instability, disrupting normal cellular functions. Histone acetylation, particularly by p300/CBP-associated factor (PCAF), is essential for maintaining genome stability and regulating cellular processes. Understanding …

TRIM24 Directs Replicative Stress Responses to Maintain ALT Telomeres via Chromatin Signaling Open

Daein Kim, Ragini Bhargava, Shih-Chun Wang, Doo‐Hyung Lee, Riya Patel , et al. · 2024

On the generation of attosecond gigawatt soft X-ray pulses through coherent Thomson backscattering Open

Qianyi Ma, Jiaxin Liu, Zhuo Pan, Xuezhi Wu, Huangang Lu , et al. · 2023

Collision between relativistic electron sheets and counter-propagating laser pulses is recognized as a promising way to produce intense attosecond X-rays through coherent Thomson backscattering (TBS). In a double-layer scheme, the electron…

APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer Open

Jennifer L. McCann, Agnese Cristini, Emily K. Law, Seo Yun Lee, Michael Tellier , et al. · 2023

The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here APOBEC3B proteomics reveal interactions with a surprising number of…

A novel role of TRIM28 B box domain in L1 retrotransposition and ORF2p-mediated cDNA synthesis Open

Qianhui Du, Emily C. Stow, Dawn LaCoste, Benjamin Freeman, Melody Baddoo , et al. · 2023

The long interspersed element 1 (LINE-1 or L1) integration is affected by many cellular factors through various mechanisms. Some of these factors are required for L1 amplification, while others either suppress or enhance specific steps dur…

Clinical and Mechanistic Implications of R-Loops in Human Leukemias Open

Seo Yun Lee, Kyle M. Miller, Jae‐Jin Kim · 2023

Genetic mutations or environmental agents are major contributors to leukemia and are associated with genomic instability. R-loops are three-stranded nucleic acid structures consisting of an RNA–DNA hybrid and a non-template single-stranded…

RAD51AP1 regulates ALT-HDR through chromatin-directed homeostasis of TERRA Open

Nicole Kaminski, Anne R. Wondisford, Youngho Kwon, Michelle Lee Lynskey, Ragini Bhargava , et al. · 2022

Looking on the horizon; potential and unique approaches to developing radiation countermeasures for deep space travel Open

Rihana S. Bokhari, Afshin Beheshti, Sarah E. Blutt, Dawn E. Bowles, David Brenner , et al. · 2022

Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce ri…

Joining the PARty: PARP Regulation of KDM5A during DNA Repair (and Transcription?) Open

Anthony Sanchez, Bethany A. Buck‐Koehntop, Kyle M. Miller · 2022

The lysine demethylase KDM5A collaborates with PARP1 and the histone variant macroH2A1.2 to modulate chromatin to promote DNA repair. Indeed, KDM5A engages poly(ADP‐ribose) (PAR) chains at damage sites through a previously uncharacterized …

Histone H2A variants: Diversifying chromatin to ensure genome integrity Open

Philipp Oberdoerffer, Kyle M. Miller · 2022

ZMYM2 restricts 53BP1 at DNA double-strand breaks to favor BRCA1 loading and homologous recombination Open

Doo‐Hyung Lee, Katja Apelt, Seong-Ok Lee, Hsin‐Ru Chan, Martijn S. Luijsterburg , et al. · 2022

An inability to repair DNA double-strand breaks (DSBs) threatens genome integrity and can contribute to human diseases, including cancer. Mammalian cells repair DSBs mainly through homologous recombination (HR) and nonhomologous end-joinin…

Making Connections: Integrative Signaling Mechanisms Coordinate DNA Break Repair in Chromatin Open

Anthony Sanchez, Doo‐Hyung Lee, Dae In Kim, Kyle M. Miller · 2021

DNA double-strand breaks (DSBs) are hazardous to genome integrity and can promote mutations and disease if not handled correctly. Cells respond to these dangers by engaging DNA damage response (DDR) pathways that are able to identify DNA b…

Bromodomain proteins: protectors against endogenous DNA damage and facilitators of genome integrity Open

Seo Yun Lee, Jae Jin Kim, Kyle M. Miller · 2021

R-loop homeostasis and cancer mutagenesis promoted by the DNA cytosine deaminase APOBEC3B Open

Jennifer L. McCann, Agnese Cristini, Emily K. Law, Seo Yun Lee, Michael Tellier , et al. · 2021

The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here, APOBEC3B proteomics reveal interactions with a surprising number o…

DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation Open

Wendan Ren, Huitao Fan, Sara A. Grimm, Jae Jin Kim, Linhui Li , et al. · 2021

DNA methylation and trimethylated histone H4 Lysine 20 (H4K20me3) constitute two important heterochromatin-enriched marks that frequently cooperate in silencing repetitive elements of the mammalian genome. However, it remains elusive how t…

Poly(ADP-ribose) binding and macroH2A mediate recruitment and functions of KDM5A at DNA lesions Open

Ramhari Kumbhar, Anthony Sanchez, Jullian Perren, Fade Gong, David Corujo , et al. · 2021

The histone demethylase KDM5A erases histone H3 lysine 4 methylation, which is involved in transcription and DNA damage responses (DDRs). While DDR functions of KDM5A have been identified, how KDM5A recognizes DNA lesion sites within chrom…

Quantifying the differential functional behavior between the medial and lateral meniscus after posterior meniscus root tears Open

Brian E. Walczak, Kyle M. Miller, Michael A. Behun, Lisa Sienkiewicz, Heather Hartwig Stokes , et al. · 2021

Meniscus tears of the knee are among the most common orthopedic knee injury. Specifically, tears of the posterior root can result in abnormal meniscal extrusion leading to decreased function and progressive osteoarthritis. Despite contempo…

Emerging roles of RNA modifications in genome integrity Open

Seo Yun Lee, Jae Jin Kim, Kyle M. Miller · 2020

Post-translational modifications of proteins are well-established participants in DNA damage response (DDR) pathways, which function in the maintenance of genome integrity. Emerging evidence is starting to reveal the involvement of modific…

A study of PCAF-mediated histone acetylation promotes replication fork degradation by MRE11 and EXO1 in BRCA-deficient cells. Kim et al Open

Jae‐Jin Kim, Seo Yun Lee, Kyle M. Miller · 2020

This is the original data set for the study entitled "PCAF-mediated histone acetylation promotes replication fork degradation by MRE11 and EXO1 in BRCA-deficient cells" and that contains all of the unprocessed microscopy images, peptide ar…

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