SMARCAL1 Resolves Replication Stress at ALT Telomeres

Cox, Kelli E.; Maréchal, Alexandre; Flynn, Rachel Litman

doi:10.1016/j.celrep.2016.02.089

Cited by 10 publications

(9 citation statements)

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“…However, they concluded that the function of SMARCAL1 was limited to ALT-positive cells (Cox et al , 2016). This group used two telomerase-positive cell lines with average telomere length possibly explaining why they did not observe a need for SMARCAL1 during telomere replication in telomerase-positive cells.…”

Section: Smarcal1mentioning

confidence: 99%

Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

Poole

Chen

2017

Critical Reviews in Biochemistry and Molecular Biology

123

104

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A large number of SNF2 family, DNA and ATP-dependent motor proteins are needed during transcription, DNA replication, and DNA repair to manipulate protein-DNA interactions and change DNA structure. SMARCAL1, ZRANB3, and HLTF are three related members of this family with specialized functions that maintain genome stability during DNA replication. These proteins are recruited to replication forks through protein-protein interactions and bind DNA using both their motor and substrate recognition domains (SRD). The SRD provides specificity to DNA structures like forks and junctions and confer DNA remodeling activity to the motor domains. Remodeling reactions include fork reversal and branch migration to promote fork stabilization, template switching, and repair. Regulation ensures these powerful activities remain controlled and restricted to damaged replication forks. Inherited mutations in SMARCAL1 cause a severe developmental disorder and mutations in ZRANB3 and HLTF are linked to cancer illustrating the importance of these enzymes in ensuring complete and accurate DNA replication. In this review, we examine how these proteins function, concentrating on their common and unique attributes and regulatory mechanisms.

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Section: Smarcal1mentioning

confidence: 99%

Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

Poole

Chen

2017

Critical Reviews in Biochemistry and Molecular Biology

123

104

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“…Telomeric repeats are hard to replicate owing to the formation of abnormal DNA structures and/or stable protein complexes, as is evident form fork stalling that is comparable to or even stronger than at other microsatellite sequences [93,94]. As discussed above, stalled forks can be readily converted into 5 0 resected, one-ended DSBs via endonucleases involved in ALT [87,95]. Since telomeres are repetitive in nature, "out of register" strand invasion or multiple template-switching events can lead to lengthening of the repetitive sequence after BIR is complete.…”

Section: Alternative Lengthening Of Telomeres Mimics Large-scale Micrmentioning

confidence: 99%

Precarious maintenance of simple DNA repeats in eukaryotes

2017

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In this review, we discuss how two evolutionarily conserved pathways at the interface of DNA replication and repair, template switching and break-induced replication, lead to the deleterious large-scale expansion of trinucleotide DNA repeats that cause numerous hereditary diseases. We highlight that these pathways, which originated in prokaryotes, may be subsequently hijacked to maintain long DNA microsatellites in eukaryotes. We suggest that the negative mutagenic outcomes of these pathways, exemplified by repeat expansion diseases, are likely outweighed by their positive role in maintaining functional repetitive regions of the genome such as telomeres and centromeres.

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“…Cells lacking SMARCAL1 are prone to accumulate DSBs [32] and patients with a biallelic deficiency in SMARCAL1 have the Schimke immunoosseous dysplasia (SIOD) disease that includes cancer predisposition [33,34]. It is interesting to note that SMARCAL1 is required to accurately and effectively replicate telomeric DNA [35][36][37]. This is the DNA of eukaryotic chromosomes that is predicted to be most sensitive to replication restart because a stalled replication fork at this location cannot be rescued by a convergent fork from another replication origin.…”

mentioning

confidence: 99%

RecG controls DNA amplification at double‐strand breaks and arrested replication forks

Azeroglu

Leach

2017

FEBS Letters

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DNA amplification is a powerful mutational mechanism that is a hallmark of cancer and drug resistance. It is therefore important to understand the fundamental pathways that cells employ to avoid over‐replicating sections of their genomes. Recent studies demonstrate that, in the absence of RecG, DNA amplification is observed at sites of DNA double‐strand break repair (DSBR) and of DNA replication arrest that are processed to generate double‐strand ends. RecG also plays a role in stabilising joint molecules formed during DSBR. We propose that RecG prevents a previously unrecognised mechanism of DNA amplification that we call reverse‐restart, which generates DNA double‐strand ends from incorrect loading of the replicative helicase at D‐loops formed by recombination, and at arrested replication forks.

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SMARCAL1 Resolves Replication Stress at ALT Telomeres

Cited by 10 publications

References 0 publications

Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

Precarious maintenance of simple DNA repeats in eukaryotes

RecG controls DNA amplification at double‐strand breaks and arrested replication forks

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