Ribonucleotides Misincorporated into DNA Act as Strand-Discrimination Signals in Eukaryotic Mismatch Repair
Articolo
Data di Pubblicazione:
2013
Citazione:
Ribonucleotides Misincorporated into DNA Act as Strand-Discrimination Signals in Eukaryotic Mismatch Repair / M.M Ghodgaonkar, F. Lazzaro, M. Olivera-Pimentel, M. Artola-Borán, P. Cejka, M.A. Reijns, A.P. Jackson, P. Plevani, M. Muzi-Falconi, J. Jiricny. - In: MOLECULAR CELL. - ISSN 1097-2765. - 50:3(2013), pp. 323-332. [10.1016/j.molcel.2013.03.019]
Abstract:
To improve replication fidelity, mismatch repair
(MMR) must detect non-Watson-Crick base pairs
and direct their repair to the nascent DNA strand. Eukaryotic
MMR in vitro requires pre-existing strand
discontinuities for initiation; consequently, it has
been postulated that MMR in vivo initiates at Okazaki
fragment termini in the lagging strand and at nicks
generated in the leading strand by the mismatchactivated
MLH1/PMS2 endonuclease. We now
show that a single ribonucleotide in the vicinity of a
mismatch can act as an initiation site for MMR in human
cell extracts and thatMMRactivation in this system
is dependent on RNase H2. As loss of RNase H2
in S.cerevisiae results in a mild MMR defect that is
reflected in increased mutagenesis, MMR in vivo
might also initiate at RNase H2-generated nicks.
We therefore propose that ribonucleotides misincoporated
during DNA replication serve as physiological
markers of the nascent DNA strand.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
M.M. Ghodgaonkar, F. Lazzaro, M. Olivera Pimentel, M. Artola Borán, P. Cejka, M.A. Reijns, A.P. Jackson, P. Plevani, M. Muzi-Falconi, J. Jiricny
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