Human RECQL1 participates in telomere maintenance

Popuri, Venkateswarlu; Hsu, Joseph K.; Khadka, Prabhat; Horvath, Kent; Liu, Yie; Croteau, Deborah L.; Bohr, Vilhelm A.

doi:10.1093/nar/gku200

Cited by 40 publications

(31 citation statements)

References 72 publications

(141 reference statements)

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“…Consistent with our observation, Popuri et al [53] have recently reported that RECQ1 associates with telomeres in ALT cells and its interaction with TRF2 regulates its helicase activity on telomeric DNA in vitro . We used a 15 nt 5’-flap substrate containing (TTAGGG) 4 sequence that has been previously reported to be bound by TRF2 [41] to ask whether RECQ1 can stimulate FEN-1 activity on telomeric DNA (Figure 8C, D).…”

Section: Resultssupporting

confidence: 93%

“…A qPCR based analysis of telomere length revealed that RECQ1-KD cells have shorter telomeres than shCTL HeLa cells (48.31 vs 52.82 kb, P= 0.038) (Figure 9E). This observation is qualitatively consistent with a recent report using Q-FISH analysis in RECQ1-depleted HeLa cells, however the magnitude of difference in telomere length in Popuri et al [53] is substantially greater and may be attributed to different assay methods used. To further characterize this system, γH2AX immunoprecipitates were analyzed.…”

Section: Resultssupporting

confidence: 92%

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RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin

Sami

Parvathaneni

et al. 2015

Biochemical Journal

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RecQ helicases are a family of highly conserved proteins that maintain genomic stability through their important roles in replication restart mechanisms. Cellular phenotypes of RECQ1 deficiency are indicative of aberrant repair of stalled replication forks, but the molecular functions of RECQ1, the most abundant of the five known human RecQ homologs, have remained poorly understood. We show that RECQ1 associates with FEN-1 in nuclear extracts and exhibits direct protein interaction in vitro. Recombinant RECQ1 significantly stimulated FEN-1 endonucleolytic cleavage of 5’-flap DNA substrates containing nontelomeric or telomeric repeat sequence. RECQ1 and FEN-1 were constitutively present at telomeres and their binding to the telomeric chromatin was enhanced following DNA damage. Telomere residence of FEN-1 was dependent on RECQ1 since depletion of RECQ1 reduced FEN-1 binding to telomeres in unperturbed cycling cells. Our results confirm a conserved collaboration of human RecQ helicases with FEN-1, and suggest both overlapping and specialized roles of RECQ1 in the processing of DNA structure intermediates proposed to arise during replication, repair and recombination.

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Section: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 92%

RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin

Sami

Parvathaneni

et al. 2015

Biochemical Journal

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“…WRN likely has a function at telomeres and can form a complex with SMARCAL1 (37); however, WRN knockdown did not cause C-circle formation. RTEL1 has at least two essential telomere functions, although we have not detected any interaction between RTEL1 and SMARCAL1 (34,38). It will be important to understand how these helicases work cooperatively to achieve successful telomere replication.…”

Section: Discussionmentioning

confidence: 81%

SMARCAL1 maintains telomere integrity during DNA replication

Poole

Zhao

Glick

et al. 2015

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

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The SMARCAL1 (SWI/SNF related, matrix-associated, actin-dependent, regulator of chromatin, subfamily A-like 1) DNA translocase is one of several related enzymes, including ZRANB3 (zinc finger, RAN-binding domain containing 3) and HLTF (helicase-like transcription factor), that are recruited to stalled replication forks to promote repair and restart replication. These enzymes can perform similar biochemical reactions such as fork reversal; however, genetic studies indicate they must have unique cellular activities. Here, we present data showing that SMARCAL1 has an important function at telomeres, which present an endogenous source of replication stress. SMARCAL1-deficient cells accumulate telomere-associated DNA damage and have greatly elevated levels of extrachromosomal telomere DNA (C-circles). Although these telomere phenotypes are often found in tumor cells using the alternative lengthening of telomeres (ALT) pathway for telomere elongation, SMARCAL1 deficiency does not yield other ALT phenotypes such as elevated telomere recombination. The activity of SMARCAL1 at telomeres can be separated from its genome-maintenance activity in bulk chromosomal replication because it does not require interaction with replication protein A. Finally, this telomere-maintenance function is not shared by ZRANB3 or HLTF. Our results provide the first identification, to our knowledge, of an endogenous source of replication stress that requires SMARCAL1 for resolution and define differences between members of this class of replication fork-repair enzymes.SMARCAL1 | telomere | replication stress | c-circle T he complete and accurate duplication of the genome in each cell-division cycle is challenged by many sources of replication stress including DNA template damage, collisions between replication and transcriptional machineries, and difficult-to-replicate DNA sequences. To overcome these challenges, cells use a multifaceted replication stress response that includes specialized enzymes that stabilize, repair, and restart stalled replication forks.Among these enzymes are members of the SNF2 family of DNA-dependent ATPases that include SMARCAL1 (SWI/SNF related, matrix-associated, actin-dependent, regulator of chromatin, subfamily A-like 1), ZRANB3 (zinc finger, RAN-binding domain containing 3), and HLTF (helicase-like transcription factor) (1). These DNA translocases bind replication fork structures, hydrolyze ATP, and perform branch migration reactions (2-11). Each of these enzymes can catalyze fork regression in vitro, although it is still unclear whether they perform this reaction in vivo (3, 4, 6-8, 11, 12). SMARCAL1 and ZRANB3 also can catalyze DNA strand annealing, disrupt displacement loop structures, and catalyze fork restoration reactions to return a regressed fork back into a normal fork structure (3,4,13).Given the overlapping biochemical activities among these translocases, it is unclear why the cell employs so many different enzymes at stalled forks. Genetic studies indicate these proteins have distinct functions. HLTF ...

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“…Recent evidence suggests a potential role of RECQ1 in telomere metabolism (43). The ability of RPA to stimulate RECQ1 removal of the catalytically inactive BamHI mutant protein bound to a DNA substrate suggested RPA may also stimulate RECQ1 displacement of the shelterin proteins TRF1 and TRF2 bound to the telomeric duplex sequence.…”

Section: Rpa Stimulates Fancj-or Recq1-catalyzed Displacement Of Trf1mentioning

confidence: 99%

Novel Function of the Fanconi Anemia Group J or RECQ1 Helicase to Disrupt Protein-DNA Complexes in a Replication Protein A-stimulated Manner

Sommers

Banerjee

Hinds

et al. 2014

Journal of Biological Chemistry

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Background: DNA unwinding by helicases is blocked by proteins bound to duplex DNA. Results: The single-stranded DNA-binding protein RPA stimulates FANCJ or RECQ1 helicase to disrupt protein-DNA complexes. Conclusion: Helicases partner with RPA to dislodge proteins bound to duplex DNA. Significance: Regulation of helicase-catalyzed protein displacement is highly relevant in cellular nucleic acid metabolic processes that require remodeling of chromatinized genomic DNA.

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Human RECQL1 participates in telomere maintenance

Cited by 40 publications

References 72 publications

RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin

RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin

SMARCAL1 maintains telomere integrity during DNA replication

Novel Function of the Fanconi Anemia Group J or RECQ1 Helicase to Disrupt Protein-DNA Complexes in a Replication Protein A-stimulated Manner

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