Roopesh Anand
University of Lugano
Publications 13
#1Ilaria Ceppi (USI: University of Lugano)
#2Sean Michael Howard (USI: University of Lugano)H-Index: 3
Last.Petr Cejka (USI: University of Lugano)H-Index: 28
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BLM or WRN helicases function with the DNA2 helicase-nuclease to resect DNA double-strand breaks and initiate homologous recombination. Upon DNA unwinding by BLM/WRN, RPA directs the DNA2 nuclease to degrade the 59-strand, revealing the 39 overhang needed for recombination. RPA bound to ssDNA also represents a barrier, explaining the need for the motor activity of DNA2 to displace RPA prior to resection. Using ensemble and single molecule biochemistry, we show that phosphorylated CtIP dramatical...
#1Jen-Wei Huang (Columbia University)H-Index: 3
#2Angelo Taglialatela (Columbia University)H-Index: 3
Last.Alberto Ciccia (Columbia University)H-Index: 20
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Homologous recombination (HR) mediates the error-free repair of DNA double-strand breaks to maintain genomic stability. HR is carried out by a complex network of DNA repair factors. Here we identify C17orf53/MCM8IP, an OB-fold containing protein that binds ssDNA, as a novel DNA repair factor involved in HR. MCM8IP-deficient cells exhibit HR defects, especially in long-tract gene conversion, occurring downstream of RAD51 loading, consistent with a role for MCM8IP in HR-dependent DNA synthesis. Mo...
#1Kristina Kasaciunaite (Leipzig University)H-Index: 2
#2Fergus Fettes (Leipzig University)H-Index: 1
Last.Ralf Seidel (WWU: University of Münster)H-Index: 37
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1 CitationsSource
#1Roopesh Anand (USI: University of Lugano)H-Index: 6
#2Arti Jasrotia (UZH: University of Zurich)H-Index: 1
Last.Petr Cejka (ETH Zurich)H-Index: 28
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Abstract DNA end resection initiates DNA double‐strand break repair by homologous recombination. MRE11‐RAD50‐NBS1 and phosphorylated CtIP perform the first resection step via MRE11‐catalyzed endonucleolytic DNA cleavage. Human NBS1, more than its homologue Xrs2 in Saccharomyces cerevisiae , is crucial for this process, highlighting complex mechanisms that regulate the MRE11 nuclease in higher eukaryotes. Using a reconstituted system, we show here that NBS1, through its FHA and BRCT domains, func...
6 CitationsSource
#1David S. YuH-Index: 20
#2Waaqo DaddachaH-Index: 3
Last.Baek KimH-Index: 35
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#1Roopesh Anand (USI: University of Lugano)H-Index: 6
#2Cosimo Pinto (UZH: University of Zurich)H-Index: 5
Last.Petr Cejka (ETH Zurich)H-Index: 28
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Abstract Accurate repair of DNA double-strand breaks (DSBs) is carried out by homologous recombination. In order to repair DNA breaks by the recombination pathway, the 5′-terminated DNA strand at DSB sites must be first nucleolytically processed to produce 3′-overhang. The process is termed DNA end resection and involves the interplay of several nuclease complexes. DNA end resection commits DSB repair to the recombination pathway including a process termed single-strand annealing, as resected DN...
5 CitationsSource
#1Cosimo Pinto (UZH: University of Zurich)H-Index: 5
#2Roopesh Anand (USI: University of Lugano)H-Index: 6
Last.Petr Cejka (ETH Zurich)H-Index: 28
view all 3 authors...
Abstract DNA end resection initiates the largely accurate repair of DNA double-strand breaks (DSBs) by homologous recombination. Specifically, recombination requires the formation of 3′ overhangs at DSB sites, which is carried out by nucleases that specifically degrade 5′-terminated DNA. In most cases, DNA end resection is a two-step process, comprising of initial short-range followed by more processive long-range resection. In this chapter, we describe selected assays that reconstitute both the...
5 CitationsSource
#1Angelo Taglialatela (CUMC: Columbia University Medical Center)H-Index: 3
#2Silvia Alvarez (CUMC: Columbia University Medical Center)H-Index: 1
Last.Alberto Ciccia (CUMC: Columbia University Medical Center)H-Index: 20
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Summary To ensure the completion of DNA replication and maintenance of genome integrity, DNA repair factors protect stalled replication forks upon replication stress. Previous studies have identified a critical role for the tumor suppressors BRCA1 and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease after replication stress. Here we show that depletion of SMARCAL1, a SNF2-family DNA translocase that remodels stalled forks, restores replication fork stability and reduces t...
67 CitationsSource
#1Waaqo Daddacha (Emory University)H-Index: 3
#2Allyson E. Koyen (Emory University)H-Index: 3
Last.David S. Yu (Emory University)H-Index: 20
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Summary DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutieres syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-i...
33 CitationsSource
#1Jun Hyun Kim (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 3
#2Malgorzata Grosbart (Erasmus University Medical Center)H-Index: 2
Last.John H.J. Petrini (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 54
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The Mre11 complex (Mre11, Rad50, and Nbs1) is integral to both DNA repair and ataxia telangiectasia mutated (ATM)-dependent DNA damage signaling. All three Mre11 complex components are essential for viability at the cellular and organismal levels. To delineate essential and non-essential Mre11 complex functions that are mediated by Nbs1, we used TALEN-based genome editing to derive Nbs1 mutant mice (Nbs1mid mice), which harbor mutations in the Mre11 interaction domain of Nbs1. Nbs1mid alleles th...
16 CitationsSource