期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 293, 期 14, 页码 5259-5269出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA117.000565
关键词
DNA helicase; DNA enzyme; DNA repair; DNA polymerase; DNA damage; DNA damage response; DNA replication; alternative end-joining; double-strand break repair; microhomology-mediated end-joining; replication fork repair; helicase; polymerase
资金
- National Institutes of Health [1R01GM115472-01]
POLQ is a unique multifunctional replication and repair gene that encodes for a N-terminal superfamily 2 helicase and a C-terminal A-family polymerase. Although the function of the polymerase domain has been investigated, little is understood regarding the helicase domain. Multiple studies have reported that polymerase -helicase (Pol-helicase) is unable to unwind DNA. However, it exhibits ATPase activity that is stimulated by single-stranded DNA, which presents a biochemical conundrum. In contrast to previous reports, we demonstrate that Pol-helicase (residues 1-894) efficiently unwinds DNA with 3-5 polarity, including DNA with 3 or 5 overhangs, blunt-ended DNA, and replication forks. Pol-helicase also efficiently unwinds RNA-DNA hybrids and exhibits a preference for unwinding the lagging strand at replication forks, similar to related HELQ helicase. Finally, we find that Pol-helicase can facilitate strand displacement synthesis by Pol-polymerase, suggesting a plausible function for the helicase domain. Taken together, these findings indicate nucleic acid unwinding as a relevant activity for Pol in replication repair.
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