Deficiency in Incisions Produced by XPF at the Site of a DNA Interstrand Cross-Link in Fanconi Anemia Cells†

Biochemistry ◽  
2007 ◽  
Vol 46 (50) ◽  
pp. 14359-14368 ◽  
Author(s):  
Kandallu R. Kumaresan ◽  
Deepa M. Sridharan ◽  
Laura W. McMahon ◽  
Muriel W. Lambert
Keyword(s):  
Fanconi Anemia ◽  
Cross Link

scholarly journals The Fanconi Anemia Pathway Promotes Replication-Dependent DNA Interstrand Cross-Link Repair

Science ◽  
2009 ◽  
Vol 326 (5960) ◽  
pp. 1698-1701 ◽  
Author(s):  
P. Knipscheer ◽  
M. Raschle ◽  
A. Smogorzewska ◽  
M. Enoiu ◽  
T. V. Ho ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Cross Link ◽  
Fanconi Anemia Pathway

scholarly journals Inactivation of ribosomal protein S27-like impairs DNA interstrand cross-link repair by destabilization of FANCD2 and FANCI

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Siyuan Sun ◽  
Hengqian He ◽  
Yuanyuan Ma ◽  
Jie Xu ◽  
Guoan Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ribosomal Protein ◽  
Cancer Cells ◽  
Fanconi Anemia ◽  
Radiation Sensitivity ◽  
Genome Integrity ◽  
Repair Pathway ◽  
Cross Link ◽  
Accelerated Degradation ◽  
Evolutionarily Conserved

Abstract Ribosomal protein S27-like (RPS27L), an evolutionarily conserved ribosomal protein and a direct p53 target, plays an important role in maintenance of genome integrity. We have previously reported that RPS27L regulates radiation sensitivity via the MDM2-p53 and MDM2-MRN-ATM axes. Whether and how RPS27L modulates DNA interstrand cross-link (ICL) repair is unknown. Here we identified that RPS27L binds to FANCD2 and FANCI, two Fanconi anemia (FA) proteins functioning in ICL repair pathway. Upon RPS27L knockdown, the levels of FANCD2 and FANCI are reduced due to accelerated degradation via p62-mediated autophagy-lysosome pathway, which is abrogated by chloroquine (CQ) treatment or Beclin 1 knockdown. Biologically, RPS27L knockdown suppresses FANCD2 foci formation and impairs ICL repair upon exposure to ICL-inducing agent mitomycin C (MMC) in lung cancer cells. This effect of MMC sensitization can be partially reversed by CQ treatment. Together, our study shows that RPS27L positively regulates ICL repair by binding with FANCD2 and FANCI to prevent their degradation via autophagy-lysosome system.

scholarly journals The Fanconi anemia complementation group C protein corrects DNA interstrand cross-link-specific apoptosis in HSC536N cells

Blood ◽  
1996 ◽  
Vol 88 (6) ◽  
pp. 2298-2305 ◽  
Author(s):  
UK Marathi ◽  
SR Howell ◽  
RA Ashmun ◽  
TP Brent
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Fanconi Anemia ◽  
Complementation Group ◽  
Cross Linking ◽  
Wild Type ◽  
Cross Link ◽  
Cycle Arrest ◽  
Protein Functions ◽  
Induced Apoptosis

Fanconi anemia (FA) cells are hypersensitive to cytotoxicity, cell cycle arrest, and chromosomal aberrations induced by DNA cross-linking agents, such as mitomycin C (MMC) and nitrogen mustard (HN2). Although MMC hypersensitivity is complemented in a subset of FA cells (complementation group C [FA-C]) by wild-type FAC cDNA, the cytoprotective mechanism is unknown. In the current study, we tested the hypothesis that FAC protein functions in the suppression of DNA interstand cross-link (ISC)-induced cell cycle arrest and apoptosis. Comparison of HN2-induced cell cycle arrest and apoptosis with those of its non-cross-linking analogs, diethylaminoethyl chloride and 2- dimethylaminoethyl chloride, delineated the DNA ISC specificity of FAC- mediated cytoprotection. Overexpression of wild-type FAC cDNA in FA-C lymphoblasts (HSC536N cell line) prevented HN2-induced growth inhibition, G2 arrest, and DNA fragmentation that is characteristic of apoptosis. In contrast cytoprotection was not conferred against the effects of the non-cross-linking mustards. Our data show that DNA ISCs induce apoptosis more potently than do DNA monoadducts and suggest that FAC suppresses specifically DNA ISC-induced apoptosis in the G2 phase of the cell cycle.

The Fanconi anemia/BRCA pathway: A coordinator of cross-link repair

2006 ◽  
Vol 312 (14) ◽  
pp. 2647-2653 ◽  
Author(s):  
Kanchan D. Mirchandani ◽  
Alan D. D'Andrea
Keyword(s):  
Fanconi Anemia ◽  
Cross Link

The Fanconi anemia/BRCA pathway is involved in DNA interstrand cross-link repair of adriamycin-resistant leukemia cells

2014 ◽  
Vol 56 (3) ◽  
pp. 755-762 ◽  
Author(s):  
Chenjiao Yao ◽  
Wei Du ◽  
Haibing Chen ◽  
Sheng Xiao ◽  
Lihua Huang ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Leukemia Cells ◽  
Cross Link

Mechanisms of Vertebrate DNA Interstrand Cross-Link Repair

2021 ◽  
Vol 90 (1) ◽  
Author(s):  
Daniel R. Semlow ◽  
Johannes C. Walter
Keyword(s):  
Fanconi Anemia ◽  
Double Helix ◽  
Bone Marrow Failure ◽  
Chemotherapy Resistance ◽  
Chemical Diversity ◽  
Annual Review ◽  
Publication Date ◽  
Cross Link ◽  
Cancer Predisposition Syndrome ◽  
Repair Pathways

DNA interstrand cross-links (ICLs) covalently connect the two strands of the double helix and are extremely cytotoxic. Defective ICL repair causes the bone marrow failure and cancer predisposition syndrome, Fanconi anemia, and upregulation of repair causes chemotherapy resistance in cancer. The central event in ICL repair involves resolving the cross-link (unhooking). In this review, we discuss the chemical diversity of ICLs generated by exogenous and endogenous agents. We then describe how proliferating and nonproliferating vertebrate cells unhook ICLs. We emphasize fundamentally new unhooking strategies, dramatic progress in the structural analysis of the Fanconi anemia pathway, and insights into how cells govern the choice between different ICL repair pathways. Throughout, we highlight the many gaps that remain in our knowledge of these fascinating DNA repair pathways. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Mechanism of DNA interstrand cross-link processing by repair nuclease FAN1

Science ◽  
2014 ◽  
Vol 346 (6213) ◽  
pp. 1127-1130 ◽  
Author(s):  
Renjing Wang ◽  
Nicole S. Persky ◽  
Barney Yoo ◽  
Ouathek Ouerfelli ◽  
Agata Smogorzewska ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Crystal Structures ◽  
Dna Adducts ◽  
Fanconi Anemia ◽  
Biochemical Data ◽  
Degenerative Diseases ◽  
Cross Link ◽  
Interstrand Cross Links ◽  
Cross Links

DNA interstrand cross-links (ICLs) are highly toxic lesions associated with cancer and degenerative diseases. ICLs can be repaired by the Fanconi anemia (FA) pathway and through FA-independent processes involving the FAN1 nuclease. In this work, FAN1-DNA crystal structures and biochemical data reveal that human FAN1 cleaves DNA successively at every third nucleotide. In vitro, this exonuclease mechanism allows FAN1 to excise an ICL from one strand through flanking incisions. DNA access requires a 5′-terminal phosphate anchor at a nick or a 1- or 2-nucleotide flap and is augmented by a 3′ flap, suggesting that FAN1 action is coupled to DNA synthesis or recombination. FAN1’s mechanism of ICL excision is well suited for processing other localized DNA adducts as well.

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