keyword
MENU ▼
Read by QxMD icon Read
search

Rif1

keyword
https://www.readbyqxmd.com/read/29234018/dynamics-of-rif1-sumoylation-is-regulated-by-pias4-in-the-maintenance-of-genomic-stability
#1
Ramesh Kumar, Cheok Chit Fang
RIF1 plays a key role in inhibiting DNA end resection and promoting NHEJ mediated DNA double stand break repair in G1. However, whether SUMOlyation may regulate RIF1 functions is still largely unknown. Here, we report that RIF1 is SUMOlyated in response to DNA damage. We identified PIAS4 as the primary SUMO E3 ligase required for the SUMOylation of RIF1 protein. Mammalian cells compromised of PIAS4 expression, show impaired RIF1 SUMOylation and defective for the disassembly of DNA damage responsive RIF1 foci...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29203878/atm-and-cdk2-control-chromatin-remodeler-csb-to-inhibit-rif1-in-dsb-repair-pathway-choice
#2
Nicole L Batenburg, John R Walker, Sylvie M Noordermeer, Nathalie Moatti, Daniel Durocher, Xu-Dong Zhu
CSB, a member of the SWI2/SNF2 superfamily, is implicated in DNA double-strand break (DSB) repair. However, how it regulates this repair process is poorly understood. Here we uncover that CSB interacts via its newly identified winged helix domain with RIF1, an effector of 53BP1, and that this interaction mediates CSB recruitment to DSBs in S phase. At DSBs, CSB remodels chromatin by evicting histones, which limits RIF1 and its effector MAD2L2 but promotes BRCA1 accumulation. The chromatin remodeling activity of CSB requires not only damage-induced phosphorylation on S10 by ATM but also cell cycle-dependent phosphorylation on S158 by cyclin A-CDK2...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29190394/acetylation-of-53bp1-dictates-the-dna-double-strand-break-repair-pathway
#3
Xiang Guo, Yongtai Bai, Meimei Zhao, Mei Zhou, Qinjian Shen, Cai-Hong Yun, Hongquan Zhang, Wei-Guo Zhu, Jiadong Wang
P53-binding protein 1 (53BP1) plays critical roles in DNA double strand break (DSB) repair by promoting non-homologous end joining (NHEJ), and loss of 53BP1 abolishes PARPi sensitivity in BRCA1-deficient cells by restoring homologous recombination (HR). 53BP1 is one of the proteins initially recruited to sites of DSBs via recognition of H4K20me2 through the Tudor-UDR domain and H2AK15ub through the UDR motif. Although extensive studies have been conducted, it remains unclear how the post-translational modification of 53BP1 affects DSB repair pathway choice...
November 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29160738/h4k20me2-distinguishes-pre-replicative-from-post-replicative-chromatin-to-appropriately-direct-dna-repair-pathway-choice-by-53bp1-rif1-mad2l2
#4
Marco Simonetta, Inge de Krijger, Judit Serrat, Nathalie Moatti, Diogo Fortunato, Liesbeth Hoekman, Onno B Bleijerveld, A F Maarten Altelaar, Jacqueline J L Jacobs
The main pathways for the repair of DNA double strand breaks (DSBs) are non-homologous end-joining (NHEJ) and homologous recombination directed repair (HDR). These operate mutually exclusive and are activated by 53BP1 and BRCA1, respectively. As HDR can only succeed in the presence of an intact copy of replicated DNA, cells employ several mechanisms to inactivate HDR in the G1 phase of cell cycle. As cells enter S-phase, these inhibitory mechanisms are released and HDR becomes active. However, during DNA replication, NHEJ and HDR pathways are both functional and non-replicated and replicated DNA regions co-exist, with the risk of aberrant HDR activity at DSBs in non-replicated DNA...
November 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29156796/downregulation-of-dna-repair-proteins-and-increased-dna-damage-in-hypoxic-colon-cancer-cells-is-a-therapeutically-exploitable-vulnerability
#5
Jennifer M J Jongen, Lizet M van der Waals, Kari Trumpi, Jamila Laoukili, Niek A Peters, Susanne J Schenning-van Schelven, Klaas M Govaert, Inne H M Borel Rinkes, Onno Kranenburg
Surgical removal of colorectal cancer (CRC) liver metastases generates areas of tissue hypoxia. Hypoxia imposes a stem-like phenotype on residual tumor cells and promotes tumor recurrence. Moreover, in primary CRC, gene expression signatures reflecting hypoxia and a stem-like phenotype are highly expressed in the aggressive Consensus Molecular Subtype 4 (CMS4). Therapeutic strategies eliminating hypoxic stem-like cells may limit recurrence following resection of primary tumors or metastases. Here we show that expression of DNA repair genes is strongly suppressed in CMS4 and inversely correlated with hypoxia-inducible factor-1 alpha (HIF1α) and HIF-2α co-expression signatures...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133916/brca2-antagonizes-classical-and-alternative-nonhomologous-end-joining-to-prevent-gross-genomic-instability
#6
Jinhua Han, Chunyan Ruan, Michael S Y Huen, Jiadong Wang, Anyong Xie, Chun Fu, Ting Liu, Jun Huang
BRCA2-deficient cells exhibit gross genomic instability, but the underlying mechanisms are not fully understood. Here we report that inactivation of BRCA2 but not RAD51 destabilizes RPA-coated single-stranded DNA (ssDNA) structures at resected DNA double-strand breaks (DSBs) and greatly enhances the frequency of nuclear fragmentation following cell exposure to DNA damage. Importantly, these BRCA2-associated deficits are fueled by the aberrant activation of classical (c)- and alternative (alt)- nonhomologous end-joining (NHEJ), and rely on the well-defined DNA damage signaling pathway involving the pro-c-NHEJ factor 53BP1 and its downstream effector RIF1...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29040764/rif1-promotes-a-repressive-chromatin-state-to-safeguard-against-endogenous-retrovirus-activation
#7
Pishun Li, Li Wang, Brian D Bennett, Jiajia Wang, Jialun Li, Yufeng Qin, Motoki Takaku, Paul A Wade, Jiemin Wong, Guang Hu
Transposable elements, including endogenous retroviruses (ERVs), constitute a large fraction of the mammalian genome. They are transcriptionally silenced during early development to protect genome integrity and aberrant transcription. However, the mechanisms that control their repression are not fully understood. To systematically study ERV repression, we carried out an RNAi screen in mouse embryonic stem cells (ESCs) and identified a list of novel regulators. Among them, Rif1 displays the strongest effect...
October 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28781144/regulation-of-repair-pathway-choice-at-two-ended-dna-double-strand-breaks
#8
REVIEW
Atsushi Shibata
A DNA double-strand break (DSB) is considered to be a critical DNA lesion because its misrepair can cause severe mutations, such as deletions or chromosomal translocations. For the precise repair of DSBs, the repair pathway that is optimal for the particular circumstance needs to be selected. Non-homologous end joining (NHEJ) functions in G1/S/G2 phase, while homologous recombination (HR) becomes active only in S/G2 phase after DNA replication. DSB end structure is another factor affecting the repair pathway...
October 2017: Mutation Research
https://www.readbyqxmd.com/read/28780613/mec1-atr-is-needed-for-extensive-telomere-elongation-in-response-to-ethanol-in-yeast
#9
Yaniv Harari, Martin Kupiec
Telomere length homeostasis is essential for cell survival. In humans, telomeres shorten as a function of age. Short telomeres are known determinants of cell senescence and longevity. The yeast Saccharomyces cerevisiae expresses telomerase and maintains a strict telomere length homeostasis during vegetative growth. We have previously reported that different environmental signals promote changes in telomere length in S. cerevisiae. In particular, exposure to ethanol induces an extensive telomere elongation response due to a reduction in RAP1 mRNA and protein levels...
August 5, 2017: Current Genetics
https://www.readbyqxmd.com/read/28700933/inhibition-of-rif1-by-scai-allows-brca1-mediated-repair
#10
Shin-Ya Isobe, Koji Nagao, Naohito Nozaki, Hiroshi Kimura, Chikashi Obuse
DNA double-strand breaks (DSBs) are repaired by either the homology-directed repair (HDR) or the non-homologous end-joining (NHEJ) pathway. RIF1 (RAP1-interacting factor homolog) was recently shown to stimulate NHEJ through an interaction with 53BP1 (p53-binding protein 1) phosphorylated at S/TQ sites, but the molecular mechanism underlying pathway choice remains unclear. Here, we show that SCAI (suppressor of cancer cell invasion) binds to 53BP1 phosphorylated at S/TP sites and facilitates HDR. Upon DNA damage, RIF1 immediately accumulates at damage sites and then gradually dissociates from 53BP1 and is subsequently replaced with SCAI...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28674277/telomere-binding-factors-in-the-regulation-of-dna-replication
#11
Hisao Masai, Yutaka Kanoh, Kenji Moriyama, Satoshi Yamazaki, Naoko Yoshizawa, Seiji Matsumoto
Recent studies have indicated new roles for telomere-binding factors in the regulation of DNA replication, not only at the telomeres but also at the arm regions of the chromosome. Among these factors, Rif1, a conserved protein originally identified in yeasts as a telomere regulator, play a major role in the spatiotemporal regulation of DNA replication during S phase. Its ability to interact with phosphatases and to create specific higher-order chromatin structures is central to the mechanism by which Rif1 exerts this function...
June 30, 2017: Genes & Genetic Systems
https://www.readbyqxmd.com/read/28604726/rif1-maintains-telomeres-and-mediates-dna-repair-by-encasing-dna-ends
#12
Stefano Mattarocci, Julia K Reinert, Richard D Bunker, Gabriele A Fontana, Tianlai Shi, Dominique Klein, Simone Cavadini, Mahamadou Faty, Maksym Shyian, Lukas Hafner, David Shore, Nicolas H Thomä, Ulrich Rass
In yeast, Rif1 is part of the telosome, where it inhibits telomerase and checkpoint signaling at chromosome ends. In mammalian cells, Rif1 is not telomeric, but it suppresses DNA end resection at chromosomal breaks, promoting repair by nonhomologous end joining (NHEJ). Here, we describe crystal structures for the uncharacterized and conserved ∼125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD), revealing an α-helical fold shaped like a shepherd's crook. We identify a high-affinity DNA-binding site in the Rif1-NTD that fully encases DNA as a head-to-tail dimer...
July 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28604711/the-anaphase-promoting-complex-impacts-repair-choice-by-protecting-ubiquitin-signalling-at-dna-damage-sites
#13
Kyungsoo Ha, Chengxian Ma, Han Lin, Lichun Tang, Zhusheng Lian, Fang Zhao, Ju-Mei Li, Bei Zhen, Huadong Pei, Suxia Han, Marcos Malumbres, Jianping Jin, Huan Chen, Yongxiang Zhao, Qing Zhu, Pumin Zhang
Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). While HDR can only occur in S/G2, NHEJ can happen in all cell cycle phases (except mitosis). How then is the repair choice made in S/G2 cells? Here we provide evidence demonstrating that APC(Cdh1) plays a critical role in choosing the repair pathways in S/G2 cells. Our results suggest that the default for all DSBs is to recruit 53BP1 and RIF1. BRCA1 is blocked from being recruited to broken ends because its recruitment signal, K63-linked poly-ubiquitin chains on histones, is actively destroyed by the deubiquitinating enzyme USP1...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28575419/telomere-shortening-triggers-a-feedback-loop-to-enhance-end-protection
#14
Chia-Wei Yang, Shun-Fu Tseng, Chia-Jung Yu, Chia-Yu Chung, Cheng-Yen Chang, Sabrina Pobiega, Shu-Chun Teng
Telomere homeostasis is controlled by both telomerase machinery and end protection. Telomere shortening induces DNA damage sensing kinases ATM/ATR for telomerase recruitment. Yet, whether telomere shortening also governs end protection is poorly understood. Here we discover that yeast ATM/ATR controls end protection. Rap1 is phosphorylated by Tel1 and Mec1 kinases at serine 731, and this regulation is stimulated by DNA damage and telomere shortening. Compromised Rap1 phosphorylation hampers the interaction between Rap1 and its interacting partner Rif1, which thereby disturbs the end protection...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28544931/role-for-rif1-interacting-partner-ddx1-in-blm-recruitment-to-dna-double-strand-breaks
#15
Lei Li, Ho-Yin Poon, Matthew R Hildebrandt, Elizabeth A Monckton, Devon R Germain, Richard P Fahlman, Roseline Godbout
Human Rap1-interacting factor 1 (RIF1) is an important player in the repair of DNA double strand breaks (DSBs). RIF1 acts downstream of 53BP1, with well-documented roles in class switch recombination in B-cells and inhibition of end resection initiation in BRCA1-defective cells. Here, we report that DEAD Box 1 (DDX1), a RNA helicase also implicated in DSB repair, interacts with RIF1, with co-localization of DDX1 and RIF1 observed throughout interphase. Recruitment of DDX1 to DSBs is dependent on RIF1, with RIF1 depletion abolishing DDX1-mediated facilitation of homologous recombination at DSBs...
July 2017: DNA Repair
https://www.readbyqxmd.com/read/28522851/mouse-rif1-is-a-regulatory-subunit-of-protein-phosphatase-1-pp1
#16
Rasa Sukackaite, Daniela Cornacchia, Malene Ringkjøbing Jensen, Philippe J Mas, Martin Blackledge, Elin Enervald, Guangyou Duan, Tania Auchynnikava, Maja Köhn, Darren J Hart, Sara B C Buonomo
Rif1 is a conserved protein that plays essential roles in orchestrating DNA replication timing, controlling nuclear architecture, telomere length and DNA repair. However, the relationship between these different roles, as well as the molecular basis of Rif1 function is still unclear. The association of Rif1 with insoluble nuclear lamina has thus far hampered exhaustive characterization of the associated protein complexes. We devised a protocol that overcomes this problem, and were thus able to discover a number of novel Rif1 interactors, involved in chromatin metabolism and phosphorylation...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273463/reversal-of-ddk-mediated-mcm-phosphorylation-by-rif1-pp1-regulates-replication-initiation-and-replisome-stability-independently-of-atr-chk1
#17
Robert C Alver, Gaganmeet Singh Chadha, Peter J Gillespie, J Julian Blow
Dbf4-dependent kinases (DDKs) are required for the initiation of DNA replication, their essential targets being the MCM2-7 proteins. We show that, in Xenopus laevis egg extracts and human cells, hyper-phosphorylation of DNA-bound Mcm4, but not phosphorylation of Mcm2, correlates with DNA replication. These phosphorylations are differentially affected by the DDK inhibitors PHA-767491 and XL413. We show that DDK-dependent MCM phosphorylation is reversed by protein phosphatase 1 (PP1) targeted to chromatin by Rif1...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28241136/tirr-regulates-53bp1-by-masking-its-histone-methyl-lysine-binding-function
#18
Pascal Drané, Marie-Eve Brault, Gaofeng Cui, Khyati Meghani, Shweta Chaubey, Alexandre Detappe, Nishita Parnandi, Yizhou He, Xiao-Feng Zheng, Maria Victoria Botuyan, Alkmini Kalousi, William T Yewdell, Christian Münch, J Wade Harper, Jayanta Chaudhuri, Evi Soutoglou, Georges Mer, Dipanjan Chowdhury
P53-binding protein 1 (53BP1) is a multi-functional double-strand break repair protein that is essential for class switch recombination in B lymphocytes and for sensitizing BRCA1-deficient tumours to poly-ADP-ribose polymerase-1 (PARP) inhibitors. Central to all 53BP1 activities is its recruitment to double-strand breaks via the interaction of the tandem Tudor domain with dimethylated lysine 20 of histone H4 (H4K20me2). Here we identify an uncharacterized protein, Tudor interacting repair regulator (TIRR), that directly binds the tandem Tudor domain and masks its H4K20me2 binding motif...
March 9, 2017: Nature
https://www.readbyqxmd.com/read/28240985/a-palb2-interacting-domain-in-rnf168-couples-homologous-recombination-to-dna-break-induced-chromatin-ubiquitylation
#19
Martijn S Luijsterburg, Dimitris Typas, Marie-Christine Caron, Wouter W Wiegant, Diana van den Heuvel, Rick A Boonen, Anthony M Couturier, Leon H Mullenders, Jean-Yves Masson, Haico van Attikum
DNA double-strand breaks (DSB) elicit a ubiquitylation cascade that controls DNA repair pathway choice. This cascade involves the ubiquitylation of histone H2A by the RNF168 ligase and the subsequent recruitment of RIF1, which suppresses homologous recombination (HR) in G1 cells. The RIF1-dependent suppression is relieved in S/G2 cells, allowing PALB2-driven HR to occur. With the inhibitory impact of RIF1 relieved, it remains unclear how RNF168-induced ubiquitylation influences HR. Here, we uncover that RNF168 links the HR machinery to H2A ubiquitylation in S/G2 cells...
February 27, 2017: ELife
https://www.readbyqxmd.com/read/28213517/the-p53-binding-protein-1-tudor-interacting-repair-regulator-complex-participates-in-the-dna-damage-response
#20
Aili Zhang, Bo Peng, Ping Huang, Junjie Chen, Zihua Gong
The 53BP1-dependent end-joining pathway plays a critical role in double strand break repair and is uniquely responsible for cellular sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPi) in BRCA1-deficient cancers. We and others have investigated the downstream effectors of 53BP1, including replication timing regulatory factor 1 (RIF1) and Pax transactivation domain-interacting protein (PTIP), in the past few years to elucidate how loss of the 53BP1-dependent repair pathway results in PARPi resistance in BRCA1 patients...
April 21, 2017: Journal of Biological Chemistry
keyword
keyword
89788
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"