Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools.
The rate of mutations in eukaryotes depends on a plethora of factors and is not immediately derived from the fidelity of DNA polymerases (Pols). Replication of chromosomes containing the anti-parallel strands of duplex DNA occurs through the copying of leading and lagging strand templates by a trio of Pols α, δ and ϵ, with the assistance of Pol ζ and Y-family Pols at difficult DNA template structures or sites of DNA damage. The parameters of the synthesis at a given location are dictated by the quality and quantity of nucleotides in the pools, replication fork architecture, transcription status, regulation of Pol switches, and structure of chromatin. The result of these transactions is a subject of survey and editing by DNA repair.
Eppley Institute for Research in Cancer and Allied Diseases, ESH 7009, 986805 Nebraska Medical Center, University of Nebraska, Omaha, NE, USA.
Irina S-R
IS
Waisertreiger
Victoria G
VG
Liston
Miriam R
MR
Menezes
Hyun-Min
HM
Kim
Kirill S
KS
Lobachev
Elena I
EI
Stepchenkova
Tahir H
TH
Tahirov
Igor B
IB
Rogozin
Youri I
YI
Pavlov
D000818:Animals; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis; D009711:Nucleotides / Q000378:metabolism*
D009711:Nucleotides; D004259:DNA-Directed DNA Polymerase