Cas9 is mostly orthogonal to human systems of DNA break sensing and repair | Sciact

Cas9 is mostly orthogonal to human systems of DNA break sensing and repair Научная публикация

Журнал

PLoS ONE
ISSN: 1932-6203

Вых. Данные

Год: 2023, Том: 18, Номер: 11, Номер статьи : e0294683, Страниц : DOI: 10.1371/journal.pone.0294683

Авторы

Maltseva Ekaterina A. ¹ , Vasil`eva Inna A. ¹ , Moor Nina A. ¹ , Kim Daria V. ^2,1 , Dyrkheeva Nadezhda S. ¹ , Kutuzov Mikhail M. ¹ , Vokhtantsev Ivan P. ¹ , Kulishova Lilya M. ¹ , Zharkov Dmitry O. ^2,1 , Lavrik Olga I. ^2,1

Организации

1	SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia
2	Novosibirsk State University, Novosibirsk, Russia

Информация о финансировании (2)

1	МИНИСТЕРСТВО НАУКИ И ВЫСШЕГО ОБРАЗОВАНИЯ РОССИЙСКОЙ ФЕДЕРАЦИИ	ПФНИ РФ (2021-2030) 0245-2021-0002
2	Российский научный фонд	РНФ №21-64-00017

CRISPR/Cas9 system is powerful gene editing tool based on the RNA-guided cleavage of target DNA. The Cas9 activity can be modulated by proteins involved in DNA damage signalling and repair due to their interaction with double- and single-strand breaks (DSB and SSB, respectively) generated by wild-type Cas9 or Cas9 nickases. Here we address the interplay between Streptococcus pyogenes Cas9 and key DNA repair factors, including poly (ADP-ribose) polymerase 1 (SSB/DSB sensor), its closest homolog poly(ADP-ribose) polymerase 2, Ku antigen (DSB sensor), DNA ligase I (SSB sensor), replication protein A (DNA duplex destabilizer), and Y-box binding protein 1 (RNA/DNA binding protein). None of those significantly affected Cas9 activity, while Cas9 efficiently shielded DSBs and SSBs from their sensors. Poly(ADP-ribosyl)ation of Cas9 detected for poly(ADP-ribose) polymerase 2 had no apparent effect on the activity. In cellulo, Cas9-dependent gene editing was independent of poly(ADP-ribose) polymerase 1. Thus, Cas9 can be regarded as an enzyme mostly orthogonal to the natural regulation of human systems of DNA break sensing and repair.

Maltseva E.A. , Vasil`eva I.A. , Moor N.A. , Kim D.V. , Dyrkheeva N.S. , Kutuzov M.M. , Vokhtantsev I.P. , Kulishova L.M. , Zharkov D.O. , Lavrik O.I.
Cas9 is mostly orthogonal to human systems of DNA break sensing and repair
PLoS ONE. 2023. V.18. N11. e0294683 . DOI: 10.1371/journal.pone.0294683 WOS Scopus PMID OpenAlex

Опубликована в печати:

29 нояб. 2023 г.

Web of science:	WOS:001142779200209
Scopus:	2-s2.0-85178223768
PMID (PubMed):	38019812
OpenAlex:	W4389128832

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