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Sean Michael Howard
University of Lugano
5Publications
3H-index
65Citations
Publications 6
Newest
#1Robin ÖzH-Index: 1
Last.Fredrik WesterlundH-Index: 25
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#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...
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#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
#2Donna R. Whelan (NYU: New York University)H-Index: 11
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DNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-p...
15 CitationsSource
#1Lepakshi Ranjha (USI: University of Lugano)H-Index: 7
#2Sean Michael Howard (USI: University of Lugano)H-Index: 3
Last.Petr Cejka (ETH Zurich)H-Index: 28
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DNA double-strand breaks arise accidentally upon exposure of DNA to radiation and chemicals or result from faulty DNA metabolic processes. DNA breaks can also be introduced in a programmed manner, such as during the maturation of the immune system, meiosis, or cancer chemo- or radiotherapy. Cells have developed a variety of repair pathways, which are fine-tuned to the specific needs of a cell. Accordingly, vegetative cells employ mechanisms that restore the integrity of broken DNA with the highe...
41 CitationsSource
#1Lepakshi Ranjha (USI: University of Lugano)H-Index: 7
#2Sean Michael Howard (USI: University of Lugano)H-Index: 3
Last.Petr Cejka (USI: University of Lugano)H-Index: 28
view all 3 authors...
3 Citations
1