RTEL1 suppresses G-quadruplex-associated R-loops at difficult-to-replicate loci in the human genome
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RTEL1 suppresses G-quadruplex-associated R-loops at difficult-to-replicate loci in the human genome. / Wu, Wei; Bhowmick, Rahul; Vogel, Ivan; Özer, Özgün; Ghisays, Fiorella; Thakur, Roshan S; Sanchez de Leon, Esther; Richter, Philipp H; Ren, Liqun; Petrini, John H; Hickson, Ian D; Liu, Ying.
I: Nature Structural & Molecular Biology, Bind 27, Nr. 5, 2020, s. 424-437.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - RTEL1 suppresses G-quadruplex-associated R-loops at difficult-to-replicate loci in the human genome
AU - Wu, Wei
AU - Bhowmick, Rahul
AU - Vogel, Ivan
AU - Özer, Özgün
AU - Ghisays, Fiorella
AU - Thakur, Roshan S
AU - Sanchez de Leon, Esther
AU - Richter, Philipp H
AU - Ren, Liqun
AU - Petrini, John H
AU - Hickson, Ian D
AU - Liu, Ying
PY - 2020
Y1 - 2020
N2 - Oncogene activation during tumorigenesis generates DNA replication stress, a known driver of genome rearrangements. In response to replication stress, certain loci, such as common fragile sites and telomeres, remain under-replicated during interphase and subsequently complete locus duplication in mitosis in a process known as 'MiDAS'. Here, we demonstrate that RTEL1 (regulator of telomere elongation helicase 1) has a genome-wide role in MiDAS at loci prone to form G-quadruplex-associated R-loops, in a process that is dependent on its helicase function. We reveal that SLX4 is required for the timely recruitment of RTEL1 to the affected loci, which in turn facilitates recruitment of other proteins required for MiDAS, including RAD52 and POLD3. Our findings demonstrate that RTEL1 is required for MiDAS and suggest that RTEL1 maintains genome stability by resolving conflicts that can arise between the replication and transcription machineries.
AB - Oncogene activation during tumorigenesis generates DNA replication stress, a known driver of genome rearrangements. In response to replication stress, certain loci, such as common fragile sites and telomeres, remain under-replicated during interphase and subsequently complete locus duplication in mitosis in a process known as 'MiDAS'. Here, we demonstrate that RTEL1 (regulator of telomere elongation helicase 1) has a genome-wide role in MiDAS at loci prone to form G-quadruplex-associated R-loops, in a process that is dependent on its helicase function. We reveal that SLX4 is required for the timely recruitment of RTEL1 to the affected loci, which in turn facilitates recruitment of other proteins required for MiDAS, including RAD52 and POLD3. Our findings demonstrate that RTEL1 is required for MiDAS and suggest that RTEL1 maintains genome stability by resolving conflicts that can arise between the replication and transcription machineries.
U2 - 10.1038/s41594-020-0408-6
DO - 10.1038/s41594-020-0408-6
M3 - Journal article
C2 - 32398827
VL - 27
SP - 424
EP - 437
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 5
ER -
ID: 241416967