Chromatin dynamics and DNA repair

10.2741/1013 ◽  
2003 ◽  
Vol 8 (6) ◽  
pp. s149-155 ◽  
Author(s):  
Vasily V Ogryzko
Keyword(s):  
Dna Repair ◽  
Chromatin Dynamics

scholarly journals DNA repair mechanisms and gametogenesis

Reproduction ◽  
2001 ◽  
pp. 31-39 ◽  
Author(s):  
WM Baarends ◽  
R van der Laan ◽  
JA Grootegoed
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Gene Knockout ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Control ◽  
Chromatin Dynamics ◽  
Dna Mismatch ◽  
Dna Repair Mechanisms ◽  
Genes Encoding ◽  
Repair Mechanisms

In mammals, there is a complex and intriguing relationship between DNA repair and gametogenesis. DNA repair mechanisms are involved not only in the repair of different types of DNA damage in developing germline cells, but also take part in the meiotic recombination process. Furthermore, the DNA repair mechanisms should tolerate mutations occurring during gametogenesis, to a limited extent. In the present review, several gametogenic aspects of DNA mismatch repair, homologous recombination repair and postreplication repair are discussed. In addition, the role of DNA damage-induced cell cycle checkpoint control is considered briefly. It appears that many genes encoding proteins that take part in DNA repair mechanisms show enhanced or specialized expression during mammalian gametogenesis, and several gene knockout mouse models show male or female infertility. On the basis of such knowledge and models, future experiments may provide more information about the precise relationship between DNA repair, chromatin dynamics, and genomic stability versus instability during gametogenesis.

scholarly journals SIRT6, a Mammalian Deacylase with Multitasking Abilities

2020 ◽  
Vol 100 (1) ◽  
pp. 145-169 ◽  
Author(s):  
Andrew R. Chang ◽  
Christina M. Ferrer ◽  
Raul Mostoslavsky
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Cellular Metabolism ◽  
Multiple Roles ◽  
Biological Processes ◽  
Repair Gene ◽  
Cellular Homeostasis ◽  
Chromatin Dynamics ◽  
Open Questions ◽  
Dna Repair Gene

Mammalian sirtuins have emerged in recent years as critical modulators of multiple biological processes, regulating cellular metabolism, DNA repair, gene expression, and mitochondrial biology. As such, they evolved to play key roles in organismal homeostasis, and defects in these proteins have been linked to a plethora of diseases, including cancer, neurodegeneration, and aging. In this review, we describe the multiple roles of SIRT6, a chromatin deacylase with unique and important functions in maintaining cellular homeostasis. We attempt to provide a framework for such different functions, for the ability of SIRT6 to interconnect chromatin dynamics with metabolism and DNA repair, and the open questions the field will face in the future, particularly in the context of putative therapeutic opportunities.

scholarly journals USP11 acts as a histone deubiquitinase functioning in chromatin reorganization during DNA repair

2019 ◽  
Vol 47 (18) ◽  
pp. 9721-9740 ◽  
Author(s):  
Xia Ting ◽  
Lu Xia ◽  
Jianguo Yang ◽  
Lin He ◽  
Wenzhe Si ◽  
...  
Keyword(s):  
Dna Repair ◽  
Chromatin Condensation ◽  
Genomic Stability ◽  
Repair Process ◽  
Histone Deacetylation ◽  
Nurd Complex ◽  
Chromatin Dynamics ◽  
Damage Response ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

Abstract How chromatin dynamics is regulated to ensure efficient DNA repair remains to be understood. Here, we report that the ubiquitin-specific protease USP11 acts as a histone deubiquitinase to catalyze H2AK119 and H2BK120 deubiquitination. We showed that USP11 is physically associated with the chromatin remodeling NuRD complex and functionally involved in DNA repair process. We demonstrated that USP11-mediated histone deubiquitination and NuRD-associated histone deacetylation coordinate to allow timely termination of DNA repair and reorganization of the chromatin structure. As such, USP11 is involved in chromatin condensation, genomic stability, and cell survival. Together, these observations indicate that USP11 is a chromatin modifier critically involved in DNA damage response and the maintenance of genomic stability.

scholarly journals The role of ubiquitin-dependent segregase p97 (VCP or Cdc48) in chromatin dynamics after DNA double strand breaks

2017 ◽  
Vol 372 (1731) ◽  
pp. 20160282 ◽  
Author(s):  
Ignacio Torrecilla ◽  
Judith Oehler ◽  
Kristijan Ramadan
Keyword(s):  
Dna Repair ◽  
Current Knowledge ◽  
Dna Lesions ◽  
Chromatin Remodelling ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Dsb Repair ◽  
Chromatin Dynamics ◽  
Strand Breaks ◽  
Signalling Molecules

DNA double strand breaks (DSBs) are the most cytotoxic DNA lesions and, if not repaired, lead to chromosomal rearrangement, genomic instability and cell death. Cells have evolved a complex network of DNA repair and signalling molecules which promptly detect and repair DSBs, commonly known as the DNA damage response (DDR). The DDR is orchestrated by various post-translational modifications such as phosphorylation, methylation, ubiquitination or SUMOylation. As DSBs are located in complex chromatin structures, the repair of DSBs is engineered at two levels: (i) at sites of broken DNA and (ii) at chromatin structures that surround DNA lesions. Thus, DNA repair and chromatin remodelling machineries must work together to efficiently repair DSBs. Here, we summarize the current knowledge of the ubiquitin-dependent molecular unfoldase/segregase p97 (VCP in vertebrates and Cdc48 in worms and lower eukaryotes) in DSB repair. We identify p97 as an essential factor that regulates DSB repair. p97-dependent extraction of ubiquitinated substrates mediates spatio-temporal protein turnover at and around the sites of DSBs, thus orchestrating chromatin remodelling and DSB repair. As p97 is a druggable target, p97 inhibition in the context of DDR has great potential for cancer therapy, as shown for other DDR components such as PARP, ATR and CHK1. This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.

scholarly journals Chromatin Dynamics during DNA Repair Revealed by Pair Correlation Analysis of Molecular Flow in the Nucleus

2014 ◽  
Vol 107 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Elizabeth Hinde ◽  
Xiangduo Kong ◽  
Kyoko Yokomori ◽  
Enrico Gratton
Keyword(s):  
Dna Repair ◽  
Correlation Analysis ◽  
Pair Correlation ◽  
Molecular Flow ◽  
Chromatin Dynamics

scholarly journals DNA Damage-Dependent Acetylation and Ubiquitination of H2AX Enhances Chromatin Dynamics

2007 ◽  
Vol 27 (20) ◽  
pp. 7028-7040 ◽  
Author(s):  
Tsuyoshi Ikura ◽  
Satoshi Tashiro ◽  
Akemi Kakino ◽  
Hiroki Shima ◽  
Naduparambil Jacob ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cell Cycle Checkpoints ◽  
Variant Form ◽  
Ionizing Irradiation ◽  
Chromatin Dynamics ◽  
Histone H2ax ◽  
Damage Response ◽  
Ubiquitin Conjugating Enzyme ◽  
Chromatin Reorganization

ABSTRACT Chromatin reorganization plays an important role in DNA repair, apoptosis, and cell cycle checkpoints. Among proteins involved in chromatin reorganization, TIP60 histone acetyltransferase has been shown to play a role in DNA repair and apoptosis. However, how TIP60 regulates chromatin reorganization in the response of human cells to DNA damage is largely unknown. Here, we show that ionizing irradiation induces TIP60 acetylation of histone H2AX, a variant form of H2A known to be phosphorylated following DNA damage. Furthermore, TIP60 regulates the ubiquitination of H2AX via the ubiquitin-conjugating enzyme UBC13, which is induced by DNA damage. This ubiquitination of H2AX requires its prior acetylation. We also demonstrate that acetylation-dependent ubiquitination by the TIP60-UBC13 complex leads to the release of H2AX from damaged chromatin. We conclude that the sequential acetylation and ubiquitination of H2AX by TIP60-UBC13 promote enhanced histone dynamics, which in turn stimulate a DNA damage response.

scholarly journals Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Hong-Yan Xie ◽  
Tai-Mei Zhang ◽  
Shu-Yuan Hu ◽  
Zhi-Ming Shao ◽  
Da-Qiang Li
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cell Survival ◽  
Zinc Finger Protein ◽  
Coiled Coil ◽  
Dna Interaction ◽  
Chromatin Dynamics ◽  
Histone H2ax ◽  
Finger Protein ◽  
Dna Repair Proteins

AbstractDecondesation of the highly compacted chromatin architecture is essential for efficient DNA repair, but how this is achieved remains largely unknown. Here, we report that microrchidia family CW-type zinc finger protein 2 (MORC2), a newly identified ATPase-dependent chromatin remodeling enzyme, is required for nucleosome destabilization after DNA damage through loosening the histone-DNA interaction. Depletion of MORC2 attenuates phosphorylated histone H2AX (γH2AX) focal formation, compromises the recruitment of DNA repair proteins, BRCA1, 53BP1, and Rad51, to sites of DNA damage, and consequently reduces cell survival following treatment with DNA-damaging chemotherapeutic drug camptothecin (CPT). Furthermore, we demonstrate that MORC2 can form a homodimer through its C-terminal coiled-coil (CC) domain, a process that is enhanced in response to CPT-induced DNA damage. Deletion of the C-terminal CC domain in MORC2 disrupts its homodimer formation and impairs its ability to destabilize histone-DNA interaction after DNA damage. Consistently, expression of dimerization-defective MORC2 mutant results in impaired the recruitment of DNA repair proteins to damaged chromatin and decreased cell survival after CPT treatment. Together, these findings uncover a new mechanism for MORC2 in modulating chromatin dynamics and DDR signaling through its c-terminal dimerization.

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