FANCJ at the FORK

Cantor, Sharon B.; Nayak, Sumeet

doi:10.1016/j.mrfmmm.2016.02.003

Cited by 13 publications

(11 citation statements)

References 81 publications

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“…Besides HR factors, SOG1 targets DNA polymerases involved in DNA replication ( POLD4 ) (69) and DNA repair [ POLK (70) and POL2A (71)], as well as genes involved in the production of deoxyribonucleotides [ TSO2 , RNR1 (72) and TK1a (73, 74)] that have been implicated in DNA repair (72, 75). Finally, several SOG1 targets remain uncharacterized, but are homologous to repair factors in other organisms, or contain domains indicating that they might have a role in DNA repair, including AT1G80850 , a gene encoding a DNA glycosylase (76), AT4G02110 , a gene encoding a BRCA1 C-terminal domain protein (77), and FANCJA , a gene homologous to a mammalian Fanconi anemia group I-like factor involved in HR repair (78) (Fig. 4).…”

Section: Resultsmentioning

confidence: 99%

SOG1 activator and MYB3R repressors regulate a complex DNA damage network in Arabidopsis

Bourbousse

Vegesna

Law

2018

Proc. Natl. Acad. Sci. U.S.A.

121

186

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SignificanceDNA damage triggers a highly conserved response that coordinates processes necessary to maintain genome integrity, including cell cycle arrest, DNA repair, and cell death. Despite the identification of primary transcription factors (TFs) that control these processes, knowledge regarding the downstream genes and regulatory networks controlled by these TFs remains poorly understood. Using Arabidopsis, we generated the first model of the DNA damage response transcriptional network, revealing 11 coexpressed gene groups with distinct biological functions and cis-regulatory features. Our characterization of this model demonstrates that SOG1 and three MYB3R TFs are, respectively, the major activator and repressors within this network, coordinating the rapid induction of DNA repair genes and TF cascades as well as the subsequent repression of cell cycle genes.

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Section: Resultsmentioning

confidence: 99%

SOG1 activator and MYB3R repressors regulate a complex DNA damage network in Arabidopsis

Bourbousse

Vegesna

Law

2018

Proc. Natl. Acad. Sci. U.S.A.

121

186

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“…DDX3 unwinds DNA, but nothing is known about its role in genome maintenance (Garbelli et al, 2011). DDX11, FANCJ, and PIF1 have been implicated in genome maintenance through roles in cohesion establishment, ICL repair, and replication fork progression (Cali et al, 2016;Cantor and Nayak, 2016;Gagou et al, 2014). Deletion of RTEL1 in mice is lethal, and hypomorphic mutations in the human gene cause Hoyeraal-Hreidarsson syndrome, which is characterized by telomere shortening, bone marrow failure, immunodeficiency, growth retardation, and microcephaly (Vannier et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

The CMG helicase bypasses DNA protein cross-links to facilitate their repair

Sparks

Gao

Räschle

et al. 2018

Preprint

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Covalent and non-covalent nucleoprotein complexes impede replication fork progression and thereby threaten genome integrity. Using Xenopus laevis egg extracts, we previously showed that when a replication fork encounters a covalent DNA-protein cross-link (DPC) on the leading strand template, the DPC is degraded to a short peptide, allowing its bypass by translesion synthesis polymerases. Strikingly, we show here that when DPC proteolysis is blocked, the replicative DNA helicase (CMG), which travels on the leading strand template, still bypasses the intact DPC. The DNA helicase RTEL1 facilitates bypass, apparently by translocating along the lagging strand template and generating single-stranded DNA downstream of the DPC.Remarkably, RTEL1 is required for efficient DPC proteolysis, suggesting that CMG bypass of a DPC normally precedes its proteolysis. RTEL1 also promotes fork progression past noncovalent protein-DNA complexes. Our data suggest a unified model for the replisome's response to nucleoprotein barriers.

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“…Other routes to elevated TLS through changes in chromatin access or RAD18 complexes have been described ( Kim et al 2014 ; Yamada et al 2014 ). We also found that the FANCJ DNA helicase has the ability to aberrantly promote TLS and suppress HR when its interaction with BRCA1 or its carboxy-terminal acetylation are disrupted ( Cantor and Nayak 2016 ; Xie et al 2010a , 2012 ). Conceivably, when not properly regulated by BRCA1, FANCJ disrupts fork-remodeling pathways and/or improves TLS efficiency by unfolding DNA secondary structures that interfere with replication.…”

Section: Rewired Fork Protection Via Tls At the Forkmentioning

confidence: 81%

Fork Protection and Therapy Resistance in Hereditary Breast Cancer

Cantor

Calvo

2017

Cold Spring Harb Symp Quant Biol

Self Cite

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The BRCA-Fanconi anemia (FA) pathway preserves the genome and suppresses cancer and is a main determinant of chemotherapeutic efficacy. The hereditary breast cancer genes BRCA1 and BRCA2 function in DNA double-strand break repair mediating distinct steps of homologous recombination (HR). More recently, independent of DNA repair, functions in the replication stress response have come to light, providing insight as to how the BRCA-FA pathway also balances genome preservation with proliferation. The BRCA-FA proteins associate with the replisome and contribute to the efficiency and recovery of replication following perturbations that slow or arrest DNA replication. Although the full repertoire of functions in the replication stress response remains to be elucidated, the function of BRCA1 and BRCA2 in protecting stalled replication forks contributes along with HR to the sensitivity of BRCA-associated tumors to chemotherapy. Moreover, chemoresistance evolves from restoration of either HR and/or fork protection. Although mechanisms underlying the restoration of HR have been characterized, it remains less clear how restoration of fork protection is achieved. Here, we outline mechanisms of “rewired” fork protection and chemotherapy resistance in BRCA cancer. We propose that mechanisms are linked to permissive replication that limits fork remodeling and therefore opportunities for fork degradation. Combating this chemoresistance mechanism will require drugs that inactivate replication bypass mechanisms.

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FANCJ at the FORK

Cited by 13 publications

References 81 publications

SOG1 activator and MYB3R repressors regulate a complex DNA damage network in Arabidopsis

SOG1 activator and MYB3R repressors regulate a complex DNA damage network in Arabidopsis

The CMG helicase bypasses DNA protein cross-links to facilitate their repair

Fork Protection and Therapy Resistance in Hereditary Breast Cancer

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