CAF-I-dependent control of degradation of the discontinuous strands during mismatch repair

Kadyrova, Lyudmila Y.; Blanko, Elena Rodriges; Kadyrov, Farid A.

doi:10.1073/pnas.1015914108

Cited by 64 publications

(94 citation statements)

References 35 publications

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“…Once repair is completed, MutSα no longer binds to DNA; CAF-1 can then freely interact with PCNA and resume chromatin assembly. Our findings that MMR delays chromatin assembly agree with recently reported data, where nucleosome deposition on heteroduplex substrates was shown to be similarly affected in the minimal reconstituted MMR system (32).…”

Section: Discussionsupporting

confidence: 93%

Interplay between mismatch repair and chromatin assembly

Schöpf

Bregenhorn

Quivy

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Single strand nicks and gaps in DNA have been reported to increase the efficiency of nucleosome loading mediated by chromatin assembly factor 1 (CAF-1). However, on mismatch-containing substrates, these strand discontinuities are utilized by the mismatch repair (MMR) system as loading sites for exonuclease 1, at which degradation of the error-containing strand commences. Because packaging of DNA into chromatin might inhibit MMR, we were interested to learn whether chromatin assembly is differentially regulated on heteroduplex and homoduplex substrates. We now show that the presence of a mismatch in a nicked plasmid substrate delays nucleosome loading in human cell extracts. Our data also suggest that, once the mismatch is removed, repair of the single-stranded gap is accompanied by efficient nucleosome loading. We postulated that the balance between MMR and chromatin assembly might be governed by proliferating cell nuclear antigen (PCNA), the processivity factor of replicative DNA polymerases, which is loaded at DNA termini and which interacts with the MSH6 subunit of the mismatch recognition factor MutSα, as well as with CAF-1. We now show that this regulation might be more complex; MutSα and CAF-1 interact not only with PCNA, but also with each other. In vivo this interaction increases during S-phase and may be controlled by the phosphorylation status of the p150 subunit of CAF-1. MMR has evolved to process mismatches arising during replication or recombination (1, 2). That its malfunction leads to cancer (3) bears witness to the importance of its role in the maintenance of genomic stability. In eukaryotes, mismatch repair (MMR) is initiated by the binding of MutSα, a heterodimer of MSH2 and MSH6, to non-Watson-Crick base pairs in DNA. Exchange of ADP for ATP then converts MutSα into a sliding clamp, which diffuses along the DNA contour, possibly together with a heterodimer of MLH1/PMS2 named MutLα, in search of free DNA termini that serve as initiation sites for exonuclease 1-catalyzed degradation of the error-containing DNA strand (1, 2).In mammalian cells, free termini are generally marked by PCNA, which helps orchestrate replication and repair DNA synthesis through interactions with key players of DNA metabolism, including MSH6 and chromatin assembly factor 1 (CAF-1) (4). The latter complex, composed of p150, p60, and p48 subunits (5), promotes rapid assembly of nucleosomes on newly replicated DNA (6).Nucleosome loading causes supercoiling, which compacts the genome and increases its stability, but which makes DNA less accessible to metabolic processes. Thus, during nucleotide excision repair, efficient processing of UV-induced DNA damage requires chromatin remodeling (7, 8) and CAF-1-mediated chromatin reassembly upon repair completion (9). Whether similar transactions take place during MMR is unknown. As the sliding function of MutSα was reported to be blocked by nucleosomes (10, 11), albeit not in all sequence contexts (12), we argued that mismatches arising during replication would have to be repaired ...

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Section: Discussionsupporting

confidence: 93%

Interplay between mismatch repair and chromatin assembly

Schöpf

Bregenhorn

Quivy

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…CAF-1-dependent nucleosome assembly probably impacts many processes that take place on the nascent DNA. Consistent with this idea, CAF-1-dependent nucleosome assembly modulates MMR (46,63). Because the MMR systemdependent flap removal (Fig.…”

Section: Genotypesupporting

confidence: 63%

“…Proteins-Human MutS␣, MutL␣, MutL␣-D699N, MutL␣-E705K, MutL␣-EA, PCNA, RFC, RPA, CAF-1, histone H3-H4 complex, and FEN1 were isolated in nearly homogeneous forms as described previously (23,25,30,46). Yeast MutS␣ containing the FLAG tag at the N terminus of its Msh6 subunit was expressed in and purified from insect Sf9 cells.…”

Section: Methodsmentioning

confidence: 99%

Evidence That the DNA Mismatch Repair System Removes 1-Nucleotide Okazaki Fragment Flaps

Kadyrova

Dahal

Kadyrov

2015

Journal of Biological Chemistry

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“…Another emerging topic is the interplay of MMR with chromatin. There are indications that MMR proteins interfere with CAF-1-dependent nucleosome loading [62] and possibly also with nucleosome repositioning, depending on sequence context [63,64]. We also identified a direct interaction between CAF-1 and MSH6, but its significance is yet to be elucidated [65].…”

Section: Discussionmentioning

confidence: 67%

Mammalian mismatch repair: error-free or error-prone?

Peña-Dı́az

Jiricny

2012

Trends in Biochemical Sciences

102

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A considerable surge of interest in the mismatch repair (MMR) system has been brought about by the discovery of a link between Lynch syndrome, an inherited predisposition to cancer of the colon and other organs, and malfunction of this key DNA metabolic pathway. This review focuses on recent advances in our understanding of the molecular mechanisms of canonical MMR, which improves replication fidelity by removing misincorporated nucleotides from the nascent DNA strand. We also discuss the involvement of MMR proteins in two other processes: trinucleotide repeat expansion and antibody maturation, in which MMR proteins are required for mutagenesis rather than for its prevention. 3

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CAF-I-dependent control of degradation of the discontinuous strands during mismatch repair

Cited by 64 publications

References 35 publications

Interplay between mismatch repair and chromatin assembly

Interplay between mismatch repair and chromatin assembly

Evidence That the DNA Mismatch Repair System Removes 1-Nucleotide Okazaki Fragment Flaps

Mammalian mismatch repair: error-free or error-prone?

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