2021
DOI: 10.1038/s41556-021-00692-z
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Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability

Abstract: Correct transcription is crucial for life. However, DNA damage severely impedes elongating RNA Polymerase II (Pol II), causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions (TBLs). However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR/cas9 screen, we identified elongation factor ELOF1 as an important factor in the tran… Show more

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Cited by 67 publications
(93 citation statements)
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“…We analyzed the fraction of CPD lesions remaining (i.e., unrepaired) after 2hr repair relative to 0hr time point for different bins along both the non-transcribed strand (NTS) and transcribed strand (TS) of ~5000 yeast genes with previously defined transcription start site (TSS) and transcription end sites (TES; based on mapped polyadenylation sites [ 37 ], see Materials and Methods ). Because there can be some variability in the absolute levels of CPDs measured using CPD-seq [ 26 ], we normalized the fraction of CPDs remaining using the alkaline gel assays ( Fig 1F and 1G ), following our published protocol [ 38 ].…”
Section: Resultsmentioning
confidence: 99%
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“…We analyzed the fraction of CPD lesions remaining (i.e., unrepaired) after 2hr repair relative to 0hr time point for different bins along both the non-transcribed strand (NTS) and transcribed strand (TS) of ~5000 yeast genes with previously defined transcription start site (TSS) and transcription end sites (TES; based on mapped polyadenylation sites [ 37 ], see Materials and Methods ). Because there can be some variability in the absolute levels of CPDs measured using CPD-seq [ 26 ], we normalized the fraction of CPDs remaining using the alkaline gel assays ( Fig 1F and 1G ), following our published protocol [ 38 ].…”
Section: Resultsmentioning
confidence: 99%
“…Our data also indicate that Set2 is important for TC-NER on the TSS-proximal side of the +1 nucleosome, even though repair in this region is largely Rad26 independent [ 40 , 65 ]. It is possible that Set2 and H3K36 methylation may also regulate Rad26-independent TC-NER, perhaps through regulating the activity of Elf1 or Rpb9 [ 5 , 38 ].…”
Section: Discussionmentioning
confidence: 99%
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“…It is often assumed that XPG is similarly recruited by its interaction with TFIIH in TC-NER, but this has not been formally shown. After initiation of TC-NER by binding of CSB to lesion-stalled Pol II, CSA is recruited, which, together with ELOF1, promotes recruitment of the UVSSA protein [ 15 , 16 , 21 , 28 ]. Subsequently, TFIIH is recruited by interaction with UVSSA, which has a similar acidic motif as XPC and XPG and binds to TFIIH through the PH domain of p62 [ 26 , 28 ].…”
Section: Xpg Activity In Nucleotide Excision Repairmentioning
confidence: 99%