@article{7605fad125ad4aa1866182b1e8952089,
title = "DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation",
abstract = "Demethylation by the AlkB dioxygenases represents an important mechanism for repair of N-alkylated nucleotides. However, little is known about their functions in mammalian cells. We report the purification of the ALKBH3 complex and demonstrate its association with the activating signal cointegrator complex (ASCC). ALKBH3 is overexpressed in various cancers, and both ALKBH3 and ASCC are important for alkylation damage resistance in these tumor cell lines. ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. In cell lines that are dependent on ALKBH3 and ASCC3 for alkylation damage resistance, loss of ALKBH3 or ASCC3 leads to increased 3-methylcytosine and reduced cell proliferation, which correlates with pH2A.X and 53BP1 foci formation. Our data provide a molecular mechanism by which ALKBH3 collaborates with ASCC to maintain genomic integrity in a cell-type specific manner.",
author = "Sebastian Dango and Nima Mosammaparast and Sowa, \{Mathew E.\} and Xiong, \{Li Jun\} and Feizhen Wu and Keyjung Park and Mark Rubin and Steve Gygi and Harper, \{J. Wade\} and Yang Shi",
note = "Funding Information: We wish to thank members of the Shi lab for helpful discussions, Huifei Lui for help with genomic DNA dot blotting, and Hank Qi for help with complex purification. S.D. is supported by a grant from the Deutsche Froschungsgemeinschaft (DFG) DA 1213/2-1. N.M. is supported by the Brigham and Women's Hospital Department of Pathology, Children's Hospital Boston Department of Laboratory Medicine, a Ruth L. Kirschstein Institutional National Research Service Award (T32-HL007627), and a Clinical Scientist Research Career Development Award (K08 CA158133). This work was supported by grants from the NIH to Y.S. (CA118487, GM071004, and GM058012) and to J.W.H. (AG011085 and GM054137). Y.S. is a cofounder of Constellation Pharmaceuticals, Inc., and is a member of its scientific advisory board. ",
year = "2011",
month = nov,
day = "4",
doi = "10.1016/j.molcel.2011.08.039",
language = "English",
volume = "44",
pages = "373--384",
journal = "Molecular cell",
issn = "1097-2765",
number = "3",
}