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Increased contribut...
Increased contribution of DNA polymerase delta to the leading strand replication in yeast with an impaired CMG helicase complex
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- Dmowski, Michal (författare)
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, Warsaw, Poland
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- Jedrychowska, Malgorzata (författare)
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, Warsaw, Poland
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- Makiela-Dzbenska, Karolina (författare)
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, Warsaw, Poland
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- Denkiewicz-Kruk, Milena (författare)
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, Warsaw, Poland
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- Sharma, Sushma (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Chabes, Andrei, Professor (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Araki, Hiroyuki (författare)
- National Institute of Genetics, 1111 Yata Shizuoka, Mishima, Japan
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- Fijalkowska, Iwona J. (författare)
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, Warsaw, Poland
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(creator_code:org_t)
- Elsevier, 2022
- 2022
- Engelska.
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Ingår i: DNA Repair. - : Elsevier. - 1568-7864 .- 1568-7856. ; 110
- Relaterad länk:
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https://umu.diva-por... (primary) (Raw object)
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Abstract
Ämnesord
Stäng
- DNA replication is performed by replisome proteins, which are highly conserved from yeast to humans. The CMG [Cdc45-Mcm2–7-GINS(Psf1–3, Sld5)] helicase unwinds the double helix to separate the leading and lagging DNA strands, which are replicated by the specialized DNA polymerases epsilon (Pol ε) and delta (Pol δ), respectively. This division of labor was confirmed by both genetic analyses and in vitro studies. Exceptions from this rule were described mainly in cells with impaired catalytic polymerase ε subunit. The central role in the recruitment and establishment of Pol ε on the leading strand is played by the CMG complex assembled on DNA during replication initiation. In this work we analyzed the consequences of impaired functioning of the CMG complex for the division labor between DNA polymerases on the two replicating strands. We showed in vitro that the GINSPsf1–1 complex poorly bound the Psf3 subunit. In vivo, we observed increased rates of L612M Pol δ-specific mutations during replication of the leading DNA strand in psf1–1 cells. These findings indicated that defective functioning of GINS impaired leading strand replication by Pol ε and necessitated involvement of Pol δ in the synthesis on this strand with a possible impact on the distribution of mutations and genomic stability. These are the first results to imply that the division of labor between the two main replicases can be severely influenced by a defective nonpolymerase subunit of the replisome.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Nyckelord
- CMG (Cdc45 Mcm2–7 GINS)
- DNA polymerase delta
- DNA polymerase epsilon
- DNA replication fidelity
- Genome stability
- Pol δ
- Pol ε
- Replication fork
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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