scholarly journals Histone Variants: Guardians of Genome Integrity

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2424
Author(s):  
Juliette Ferrand ◽  
Beatrice Rondinelli ◽  
Sophie E. Polo
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Genome Stability ◽  
Current Knowledge ◽  
Histone Variants ◽  
Chromatin Dynamics ◽  
Open Questions ◽  
Damage Repair ◽  
Pathological Development ◽  
Chromatin Integrity

Chromatin integrity is key for cell homeostasis and for preventing pathological development. Alterations in core chromatin components, histone proteins, recently came into the spotlight through the discovery of their driving role in cancer. Building on these findings, in this review, we discuss how histone variants and their associated chaperones safeguard genome stability and protect against tumorigenesis. Accumulating evidence supports the contribution of histone variants and their chaperones to the maintenance of chromosomal integrity and to various steps of the DNA damage response, including damaged chromatin dynamics, DNA damage repair, and damage-dependent transcription regulation. We present our current knowledge on these topics and review recent advances in deciphering how alterations in histone variant sequence, expression, and deposition into chromatin fuel oncogenic transformation by impacting cell proliferation and cell fate transitions. We also highlight open questions and upcoming challenges in this rapidly growing field.

scholarly journals First person – Fabiola García Fernández

2021 ◽  
Vol 134 (6) ◽  
pp. jcs258591
Keyword(s):  
Dna Damage ◽  
Genome Stability ◽  
Chromosome Structure ◽  
Early Career ◽  
First Person ◽  
Saint Louis ◽  
Early Career Researchers ◽  
Damage Repair ◽  
Damage Response ◽  
Selection Of

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Fabiola García Fernández is first author on ‘Modified chromosome structure casued by phosphomimetic H2A modulates the DNA damage response by increasing chromatin mobility in yeast’, published in JCS. Fabiola is a PhD student in the lab of Emmanuelle Fabre at Institut de recherche Saint-Louis, Université de Paris, France, investigating DNA damage repair and genome stability.

scholarly journals HP1β Chromo Shadow Domain facilitates H2A ubiquitination for BRCA1 recruitment at DNA double-strand breaks

2022 ◽  
Author(s):  
Tej Pandita ◽  
Vijay Kumari Charaka ◽  
Sharmistha Chakraborty ◽  
Chi-Lin Tsai ◽  
Xiaoyan Wang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genome Stability ◽  
Strand Break ◽  
Dna Double Strand Breaks ◽  
Dsb Repair ◽  
Strand Breaks ◽  
Damage Repair ◽  
Dna Double Strand Break ◽  
Assembly Factor ◽  
Chromo Shadow Domain

Efficient DNA double strand break (DSB) repair by homologous recombination (HR), as orchestrated by histone and non-histone proteins, is critical to genome stability, replication, transcription, and cancer avoidance. Here we report that Heterochromatin Protein1 beta (HP1β) acts as a key component of the HR DNA resection step by regulating BRCA1 enrichment at DNA damage sites, a function largely dependent on the HP1β chromo shadow domain (CSD). HP1β itself is enriched at DSBs within gene-rich regions through a CSD interaction with Chromatin Assembly Factor 1 (CAF1) and HP1β depletion impairs subsequent BRCA1 enrichment. An added interaction of the HP1β CSD with the Polycomb Repressor Complex 1 ubiquitinase component RING1A facilitates BRCA1 recruitment by increasing H2A lysine 118-119 ubiquitination, a marker for BRCA1 recruitment. Our findings reveal that HP1β interactions, mediated through its CSD with RING1A, promote H2A ubiquitination and facilitate BRCA1 recruitment at DNA damage sites, a critical step in DSB repair by the HR pathway. These collective results unveil how HP1β is recruited to DSBs in gene-rich regions and how HP1β subsequently promotes BRCA1 recruitment to further HR DNA damage repair by stimulating CtIP-dependent resection.

scholarly journals The Mysteries around the BCL-2 Family Member BOK

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1638
Author(s):  
Raed Shalaby ◽  
Hector Flores-Romero ◽  
Ana J. García-Sáez
Keyword(s):  
Family Member ◽  
Cell Fate ◽  
Current Knowledge ◽  
Structural Features ◽  
Special Focus ◽  
Cellular Functions ◽  
Open Questions ◽  
Apoptotic Protein ◽  
Evolutionarily Conserved ◽  
Apoptosis Regulation

BOK is an evolutionarily conserved BCL-2 family member that resembles the apoptotic effectors BAK and BAX in sequence and structure. Based on these similarities, BOK has traditionally been classified as a BAX-like pro-apoptotic protein. However, the mechanism of action and cellular functions of BOK remains controversial. While some studies propose that BOK could replace BAK and BAX to elicit apoptosis, others attribute to this protein an indirect way of apoptosis regulation. Adding to the debate, BOK has been associated with a plethora of non-apoptotic functions that makes this protein unpredictable when dictating cell fate. Here, we compile the current knowledge and open questions about this paradoxical protein with a special focus on its structural features as the key aspect to understand BOK biological functions.

scholarly journals Autophagy Roles in Genome Maintenance

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1793 ◽  
Author(s):  
Susanna Ambrosio ◽  
Barbara Majello
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Dna Damage Response ◽  
Current Knowledge ◽  
Response To Therapy ◽  
Genome Integrity ◽  
Genome Maintenance ◽  
Damage Response ◽  
Cancer Cell Survival ◽  
Fate Decision

In recent years, a considerable correlation has emerged between autophagy and genome integrity. A range of mechanisms appear to be involved where autophagy participates in preventing genomic instability, as well as in DNA damage response and cell fate decision. These initial findings have attracted particular attention in the context of malignancy; however, the crosstalk between autophagy and DNA damage response is just beginning to be explored and key questions remain that need to be addressed, to move this area of research forward and illuminate the overall consequence of targeting this process in human therapies. Here we present current knowledge on the complex crosstalk between autophagy and genome integrity and discuss its implications for cancer cell survival and response to therapy.

XPC multifaceted roles beyond DNA damage repair: p53-dependent and p53-independent functions of XPC in cell fate decisions

2021 ◽  
pp. 108400
Author(s):  
Abir Zebian ◽  
Maya El-Dor ◽  
Abdullah Shaito ◽  
Frédéric Mazurier ◽  
Hamid Reza Rezvani ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Dna Damage Repair ◽  
Cell Fate Decisions ◽  
Damage Repair ◽  
Independent Functions

Chromatin plasticity: A versatile landscape that underlies cell fate and identity

Science ◽  
2018 ◽  
Vol 361 (6409) ◽  
pp. 1332-1336 ◽  
Author(s):  
Tejas Yadav ◽  
Jean-Pierre Quivy ◽  
Geneviève Almouzni
Keyword(s):  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Histone Variants ◽  
Proper Function ◽  
Cell Fate Decision ◽  
Chromatin Dynamics ◽  
Pathological Conditions ◽  
Technological Advances ◽  
Potential Therapeutic Application ◽  
Fate Decision

During development and throughout life, a variety of specialized cells must be generated to ensure the proper function of each tissue and organ. Chromatin plays a key role in determining cellular state, whether totipotent, pluripotent, multipotent, or differentiated. We highlight chromatin dynamics involved in the generation of pluripotent stem cells as well as their influence on cell fate decision and reprogramming. We focus on the capacity of histone variants, chaperones, modifications, and heterochromatin factors to influence cell identity and its plasticity. Recent technological advances have provided tools to elucidate the underlying chromatin dynamics for a better understanding of normal development and pathological conditions, with avenues for potential therapeutic application.

scholarly journals LncRNA NEAT1 in Paraspeckles: A Structural Scaffold for Cellular DNA Damage Response Systems?

2020 ◽  
Vol 6 (3) ◽  
pp. 26 ◽  
Author(s):  
Elisa Taiana ◽  
Domenica Ronchetti ◽  
Katia Todoerti ◽  
Lucia Nobili ◽  
Pierfrancesco Tassone ◽  
...  
Keyword(s):  
Dna Damage ◽  
Current Knowledge ◽  
Nuclear Bodies ◽  
Cellular Functions ◽  
Damage Repair ◽  
Non Coding Rna ◽  
Response Systems ◽  
Cellular Dna ◽  
Lncrna Neat1 ◽  
Long Non Coding Rna

Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) reported to be frequently deregulated in various types of cancers and neurodegenerative processes. NEAT1 is an indispensable structural component of paraspeckles (PSs), which are dynamic and membraneless nuclear bodies that affect different cellular functions, including stress response. Furthermore, increasing evidence supports the crucial role of NEAT1 and essential structural proteins of PSs (PSPs) in the regulation of the DNA damage repair (DDR) system. This review aims to provide an overview of the current knowledge on the involvement of NEAT1 and PSPs in DDR, which might strengthen the rationale underlying future NEAT1-based therapeutic options in tumor and neurodegenerative diseases.

scholarly journals The Importance of ATM and ATR in Physcomitrella patens DNA Damage Repair, Development, and Gene Targeting

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 752
Author(s):  
Martin Martens ◽  
Ralf Horres ◽  
Edelgard Wendeler ◽  
Bernd Reiss
Keyword(s):  
Dna Damage ◽  
Gene Targeting ◽  
Genome Stability ◽  
Physcomitrella Patens ◽  
Dna Damage Repair ◽  
Transcriptional Response ◽  
Vegetative Development ◽  
Dsb Repair ◽  
Yeast Saccharomyces Cerevisiae ◽  
Damage Repair

Coordinated by ataxia-telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR), two highly conserved kinases, DNA damage repair ensures genome integrity and survival in all organisms. The Arabidopsis thaliana (A. thaliana) orthologues are well characterized and exhibit typical mammalian characteristics. We mutated the Physcomitrella patens (P. patens) PpATM and PpATR genes by deleting functionally important domains using gene targeting. Both mutants showed growth abnormalities, indicating that these genes, particularly PpATR, are important for normal vegetative development. ATR was also required for repair of both direct and replication-coupled double-strand breaks (DSBs) and dominated the transcriptional response to direct DSBs, whereas ATM was far less important, as shown by assays assessing resistance to DSB induction and SuperSAGE-based transcriptomics focused on DNA damage repair genes. These characteristics differed significantly from the A. thaliana genes but resembled those in yeast (Saccharomyces cerevisiae). PpATR was not important for gene targeting, pointing to differences in the regulation of gene targeting and direct DSB repair. Our analysis suggests that ATM and ATR functions can be substantially diverged between plants. The differences in ATM and ATR reflect the differences in DSB repair pathway choices between A. thaliana and P. patens, suggesting that they represent adaptations to different demands for the maintenance of genome stability.

One ring to bind them – Cohesin’s interaction with chromatin fibers

2019 ◽  
Vol 63 (1) ◽  
pp. 167-176 ◽  
Author(s):  
Macarena Moronta-Gines ◽  
Thomas R.H. van Staveren ◽  
Kerstin S. Wendt
Keyword(s):  
Dna Damage ◽  
Genetic Information ◽  
Current Knowledge ◽  
Current Model ◽  
Chromatin Fiber ◽  
Eukaryotic Cells ◽  
Cohesin Complex ◽  
Multiprotein Complex ◽  
Damage Repair ◽  
Order Structures

Abstract In the nuclei of eukaryotic cells, the genetic information is organized at several levels. First, the DNA is wound around the histone proteins, to form a structure termed as chromatin fiber. This fiber is then arranged into chromatin loops that can cluster together and form higher order structures. This packaging of chromatin provides on one side compaction but also functional compartmentalization. The cohesin complex is a multifunctional ring-shaped multiprotein complex that organizes the chromatin fiber to establish functional domains important for transcriptional regulation, help with DNA damage repair, and ascertain stable inheritance of the genome during cell division. Our current model for cohesin function suggests that cohesin tethers chromatin strands by topologically entrapping them within its ring. To achieve this, cohesin’s association with chromatin needs to be very precisely regulated in timing and position on the chromatin strand. Here we will review the current insight in when and where cohesin associates with chromatin and which factors regulate this. Further, we will discuss the latest insights into where and how the cohesin ring opens to embrace chromatin and also the current knowledge about the ‘exit gates’ when cohesin is released from chromatin.

Sign in / Sign up

Export Citation Format

Share Document