Person:
Yusufzai, Timur

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Yusufzai

First Name

Timur

Name

Yusufzai, Timur
Author's Publications: search.filters.isAuthorOfPublication.1057a7d3-7299-4db0-a18c-cfe5230a85ad

Search Results

Now showing 1 - 5 of 5
  • Thumbnail Image
    Publication
    Introducing Rare Diseases
    (Landes Bioscience, 2013) Szajner, Patricia; Yusufzai, Timur
  • Thumbnail Image
    Publication
    Homologous recombination-deficient tumors are hyper-dependent on POLQ-mediated repair
    (2015) Ceccaldi, Raphael; Liu, Jessica; Amunugama, Ravindra; Hajdu, Ildiko; Primack, Benjamin; Petalcorin, Mark I.R.; O'Connor, Kevin W.; Konstantinopoulos, Panagiotis; Elledge, Stephen J.; Boulton, Simon J.; Yusufzai, Timur; D'Andrea, Alan
  • Thumbnail Image
    Publication
    The Chromatin Remodeling Factor CHD5 Is a Transcriptional Repressor of WEE1
    (Public Library of Science, 2014) Quan, Jinhua; Adelmant, Guillaume; Marto, Jarrod; Look, A. Thomas; Yusufzai, Timur
    Loss of the chromatin remodeling ATPase CHD5 has been linked to the progression of neuroblastoma tumors, yet the underlying mechanisms behind the tumor suppressor role of CHD5 are unknown. In this study, we purified the human CHD5 complex and found that CHD5 is a component of the full NuRD transcriptional repressor complex, which also contains methyl-CpG binding proteins and histone deacetylases. The CHD5/NuRD complex appears mutually exclusive with the related CHD4/NuRD complex as overexpression of CHD5 results in loss of the CHD4 protein in cells. Following a search for genes that are regulated by CHD5 in neuroblastoma cells, we found that CHD5 binds to and represses the G2/M checkpoint gene WEE1. Reintroduction of CHD5 into neuroblastoma cells represses WEE1 expression, demonstrating that CHD5 can function as a repressor in cells. A catalytically inactive mutant version of CHD5 is able to associate with a NuRD cofactor but fails to repress transcription. Our study shows that CHD5 is a NuRD-associated transcriptional repressor and identifies WEE1 as one of the CHD5-regulated genes that may link CHD5 to tumor suppression.
  • Thumbnail Image
    Publication
    HARP preferentially co-purifies with RPA bound to DNA-PK and blocks RPA phosphorylation
    (Landes Bioscience, 2014) Quan, Jinhua; Yusufzai, Timur
    The HepA-related protein (HARP/SMARCAL1) is an ATP-dependent annealing helicase that is capable of rewinding DNA structures that are stably unwound due to binding of the single-stranded DNA (ssDNA)-binding protein Replication Protein A (RPA). HARP has been implicated in maintaining genome integrity through its role in DNA replication and repair, two processes that generate RPA-coated ssDNA. In addition, mutations in HARP cause a rare disease known as Schimke immuno-osseous dysplasia. In this study, we purified HARP containing complexes with the goal of identifying the predominant factors that stably associate with HARP. We found that HARP preferentially interacts with RPA molecules that are bound to the DNA-dependent protein kinase (DNA-PK). We also found that RPA is phosphorylated by DNA-PK in vitro, while the RPA-HARP complexes are not. Our results suggest that, in addition to its annealing helicase activity, which eliminates the natural binding substrate for RPA, HARP blocks the phosphorylation of RPA by DNA-PK.
  • Thumbnail Image
    Publication
    Annealing helicase HARP closes RPA-stabilized DNA bubbles non-processively
    (Oxford University Press, 2017) Burnham, Daniel R.; Nijholt, Bas; De Vlaminck, Iwijn; Quan, Jinhua; Yusufzai, Timur; Dekker, Cees
    Abstract We investigate the mechanistic nature of the Snf2 family protein HARP, mutations of which are responsible for Schimke immuno-osseous dysplasia. Using a single-molecule magnetic tweezers assay, we construct RPA-stabilized DNA bubbles within torsionally constrained DNA to investigate the annealing action of HARP on a physiologically relevant substrate. We find that HARP closes RPA-stabilized bubbles in a slow reaction, taking on the order of tens of minutes for ∼600 bp of DNA to be re-annealed. The data indicate that DNA re-anneals through the removal of RPA, which is observed as clear steps in the bubble-closing traces. The dependence of the closing rate on both ionic strength and HARP concentration indicates that removal of RPA occurs via an association-dissociation mechanism where HARP does not remain associated with the DNA. The enzyme exhibits classical Michaelis–Menten kinetics and acts cooperatively with a Hill coefficient of 3 ± 1. Our work also allows the determination of some important features of RPA-bubble structures at low supercoiling, including the existence of multiple bubbles and that RPA molecules are mis-registered on the two strands.