000			01789nam a2200241Ia 4500
003			MX-MdCICY
005			20250625162459.0
040			_cCICY
090			_aB-20976
245	1	0	_aHydrolytic endonucleolytic ribozyme (HYER)is programmable for sequence-specific DNA cleavage
490	0		_vScience, 383(6682), p.eadh4859, 2024
520	3		_aRibozymes are catalytic RNAs with diverse functions including self-splicing and polymerization. This work aims to discover natural ribozymes that behave as hydrolytic and sequence-specific DNA endonucleases, which could be repurposed as DNA manipulation tools. Focused on bacterial group II-C introns, we found that many systems without intron-encoded protein propagate multiple copies in their resident genomes. These introns, named HYdrolytic Endonucleolytic Ribozymes (HYERs), cleaved RNA, single-stranded DNA, bubbled double-stranded DNA (dsDNA), and plasmids in vitro. HYER1 generated dsDNA breaks in the mammalian genome. Cryo-electron microscopy analysis revealed a homodimer structure for HYER1, where each monomer contains a Mg2+-dependent hydrolysis pocket and captures DNA complementary to the target recognition site (TRS). Rational designs including TRS extension, recruiting sequence insertion, and heterodimerization yielded engineered HYERs showing improved specificity and flexibility for DNA manipulation.
700	1	2	_aLiu, Z. X.
700	1	2	_aZhang, S.
700	1	2	_aZhu, H. Z.
700	1	2	_aChen, Z. H.
700	1	2	_aYang, Y.
700	1	2	_aLi, L. Q.
700	1	2	_aLiu, J. J. G.
856	4	0	_uhttps://drive.google.com/file/d/1jcc4PS2QyAsI8_GS0BM41Q0INR7ICdlz/view?usp=drivesdk _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
942			_2Loc _cREF1
008			250602s9999 xx |||||s2 |||| ||und|d
999			_c55055 _d55055