Atl1 Regulates Choice between Global Genome and Transcription-Coupled Repair of O 6-Alkylguanines

Vitaly F. Latypov; Julie L. Tubbs; Amanda J. Watson; Andrew S. Marriott; Gail McGown; Mary Thorncroft; Oliver J. Wilkinson; Pattama Senthong; Amna Butt; Andrew S. Arvai; Christopher L. Millington; Andrew C. Povey; David M. Williams; Mauro F. Santibanez-Koref; John A. Tainer; Geoffrey P. Margison

doi:10.1016/j.molcel.2012.04.028

Atl1 Regulates Choice between Global Genome and Transcription-Coupled Repair of O 6-Alkylguanines

Vitaly F. Latypov, Julie L. Tubbs, Amanda J. Watson, Andrew S. Marriott, Gail McGown, Mary Thorncroft, Oliver J. Wilkinson, Pattama Senthong, Amna Butt, Andrew S. Arvai, Christopher L. Millington, Andrew C. Povey, David M. Williams, Mauro F. Santibanez-Koref, John A. Tainer, Geoffrey P. Margison

Research output: Contribution to journal › Article › peer-review

Abstract

Nucleotide excision repair (NER) has long been known to remove DNA lesions induced by chemical carcinogens, and the molecular mechanism has been partially elucidated. Here we demonstrate that in Schizosaccharomyces pombe a DNA recognition protein, alkyltransferase-like 1 (Atl1), can play a pivotal role in selecting a specific NER pathway, depending on the nature of the DNA modification. The relative ease of dissociation of Atl1 from DNA containing small O 6-alkylguanines allows accurate completion of global genome repair (GGR), whereas strong Atl1 binding to bulky O 6-alkylguanines blocks GGR, stalls the transcription machinery, and diverts the damage to transcription-coupled repair. Our findings redraw the initial stages of the NER process in those organisms that express an alkyltransferase-like gene and raise the question of whether or not O 6-alkylguanine lesions that are poor substrates for the alkyltransferase proteins in higher eukaryotes might, by analogy, signal such lesions for repair by NER. © 2012 Elsevier Inc.

Original language	English
Pages (from-to)	50-60
Number of pages	10
Journal	Molecular Cell
Volume	47
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2012.04.028
Publication status	Published - 13 Jul 2012

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Latypov, V. F., Tubbs, J. L., Watson, A. J., Marriott, A. S., McGown, G., Thorncroft, M., Wilkinson, O. J., Senthong, P., Butt, A., Arvai, A. S., Millington, C. L., Povey, A. C., Williams, D. M., Santibanez-Koref, M. F., Tainer, J. A., & Margison, G. P. (2012). Atl1 Regulates Choice between Global Genome and Transcription-Coupled Repair of O 6-Alkylguanines. Molecular Cell, 47(1), 50-60. https://doi.org/10.1016/j.molcel.2012.04.028

@article{f1393d9a4fcf4c289c4e2cf13be0aa16,

title = "Atl1 Regulates Choice between Global Genome and Transcription-Coupled Repair of O 6-Alkylguanines",

abstract = "Nucleotide excision repair (NER) has long been known to remove DNA lesions induced by chemical carcinogens, and the molecular mechanism has been partially elucidated. Here we demonstrate that in Schizosaccharomyces pombe a DNA recognition protein, alkyltransferase-like 1 (Atl1), can play a pivotal role in selecting a specific NER pathway, depending on the nature of the DNA modification. The relative ease of dissociation of Atl1 from DNA containing small O 6-alkylguanines allows accurate completion of global genome repair (GGR), whereas strong Atl1 binding to bulky O 6-alkylguanines blocks GGR, stalls the transcription machinery, and diverts the damage to transcription-coupled repair. Our findings redraw the initial stages of the NER process in those organisms that express an alkyltransferase-like gene and raise the question of whether or not O 6-alkylguanine lesions that are poor substrates for the alkyltransferase proteins in higher eukaryotes might, by analogy, signal such lesions for repair by NER. {\textcopyright} 2012 Elsevier Inc.",

author = "Latypov, {Vitaly F.} and Tubbs, {Julie L.} and Watson, {Amanda J.} and Marriott, {Andrew S.} and Gail McGown and Mary Thorncroft and Wilkinson, {Oliver J.} and Pattama Senthong and Amna Butt and Arvai, {Andrew S.} and Millington, {Christopher L.} and Povey, {Andrew C.} and Williams, {David M.} and Santibanez-Koref, {Mauro F.} and Tainer, {John A.} and Margison, {Geoffrey P.}",

year = "2012",

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doi = "10.1016/j.molcel.2012.04.028",

language = "English",

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pages = "50--60",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

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Latypov, VF, Tubbs, JL, Watson, AJ, Marriott, AS, McGown, G, Thorncroft, M, Wilkinson, OJ, Senthong, P, Butt, A, Arvai, AS, Millington, CL, Povey, AC, Williams, DM, Santibanez-Koref, MF, Tainer, JA & Margison, GP 2012, 'Atl1 Regulates Choice between Global Genome and Transcription-Coupled Repair of O 6-Alkylguanines', Molecular Cell, vol. 47, no. 1, pp. 50-60. https://doi.org/10.1016/j.molcel.2012.04.028

TY - JOUR

T1 - Atl1 Regulates Choice between Global Genome and Transcription-Coupled Repair of O 6-Alkylguanines

AU - Latypov, Vitaly F.

AU - Tubbs, Julie L.

AU - Watson, Amanda J.

AU - Marriott, Andrew S.

AU - McGown, Gail

AU - Thorncroft, Mary

AU - Wilkinson, Oliver J.

AU - Senthong, Pattama

AU - Butt, Amna

AU - Arvai, Andrew S.

AU - Millington, Christopher L.

AU - Povey, Andrew C.

AU - Williams, David M.

AU - Santibanez-Koref, Mauro F.

AU - Tainer, John A.

AU - Margison, Geoffrey P.

PY - 2012/7/13

Y1 - 2012/7/13

N2 - Nucleotide excision repair (NER) has long been known to remove DNA lesions induced by chemical carcinogens, and the molecular mechanism has been partially elucidated. Here we demonstrate that in Schizosaccharomyces pombe a DNA recognition protein, alkyltransferase-like 1 (Atl1), can play a pivotal role in selecting a specific NER pathway, depending on the nature of the DNA modification. The relative ease of dissociation of Atl1 from DNA containing small O 6-alkylguanines allows accurate completion of global genome repair (GGR), whereas strong Atl1 binding to bulky O 6-alkylguanines blocks GGR, stalls the transcription machinery, and diverts the damage to transcription-coupled repair. Our findings redraw the initial stages of the NER process in those organisms that express an alkyltransferase-like gene and raise the question of whether or not O 6-alkylguanine lesions that are poor substrates for the alkyltransferase proteins in higher eukaryotes might, by analogy, signal such lesions for repair by NER. © 2012 Elsevier Inc.

AB - Nucleotide excision repair (NER) has long been known to remove DNA lesions induced by chemical carcinogens, and the molecular mechanism has been partially elucidated. Here we demonstrate that in Schizosaccharomyces pombe a DNA recognition protein, alkyltransferase-like 1 (Atl1), can play a pivotal role in selecting a specific NER pathway, depending on the nature of the DNA modification. The relative ease of dissociation of Atl1 from DNA containing small O 6-alkylguanines allows accurate completion of global genome repair (GGR), whereas strong Atl1 binding to bulky O 6-alkylguanines blocks GGR, stalls the transcription machinery, and diverts the damage to transcription-coupled repair. Our findings redraw the initial stages of the NER process in those organisms that express an alkyltransferase-like gene and raise the question of whether or not O 6-alkylguanine lesions that are poor substrates for the alkyltransferase proteins in higher eukaryotes might, by analogy, signal such lesions for repair by NER. © 2012 Elsevier Inc.

U2 - 10.1016/j.molcel.2012.04.028

DO - 10.1016/j.molcel.2012.04.028

M3 - Article

SN - 1097-2765

VL - 47

SP - 50

EP - 60

JO - Molecular Cell

JF - Molecular Cell

IS - 1

ER -

Atl1 Regulates Choice between Global Genome and Transcription-Coupled Repair of O 6-Alkylguanines

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