Structural highlights
Function
DPOZ_YEAST Nonessential DNA polymerase. Required for DNA damage induced mutagenesis. Involved in DNA repair, mitochondrial DNA repair and translesion synthesis. Translesion synthesis in S.cerevisiae may use a specialized DNA polymerase that is not required for other DNA replicative processes. Has a role in the bypass of abasic (AP) sites. Highly inefficient in incorporating nucleotides opposite the AP site, but efficiently extends from nucleotides, particularly an A, inserted opposite the lesion.[1] [2] [3] [4]
Publication Abstract from PubMed
Rev1-Polzeta-dependent translesion synthesis (TLS) of DNA is crucial for maintaining genome integrity. To elucidate the mechanism by which the two polymerases cooperate in TLS, we determined the cryogenic electron microscopic structure of the Saccharomyces cerevisiae Rev1-Polzeta holocomplex in the act of DNA synthesis (3.53 A). We discovered that a composite N-helix-BRCT module in Rev1 is the keystone of Rev1-Polzeta cooperativity, interacting directly with the DNA template-primer and with the Rev3 catalytic subunit of Polzeta. The module is positioned akin to the polymerase-associated domain in Y-family TLS polymerases and is set ideally to interact with PCNA. We delineate the full extent of interactions that the carboxy-terminal domain of Rev1 makes with Polzeta and identify potential new druggable sites to suppress chemoresistance from first-line chemotherapeutics. Collectively, our results provide fundamental new insights into the mechanism of cooperativity between Rev1 and Polzeta in TLS.
Cryo-EM structure of the Rev1-Polzeta holocomplex reveals the mechanism of their cooperativity in translesion DNA synthesis.,Malik R, Johnson RE, Ubarretxena-Belandia I, Prakash L, Prakash S, Aggarwal AK Nat Struct Mol Biol. 2024 Sep;31(9):1394-1403. doi: 10.1038/s41594-024-01302-w. , Epub 2024 May 8. PMID:38720088[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Haracska L, Unk I, Johnson RE, Johansson E, Burgers PM, Prakash S, Prakash L. Roles of yeast DNA polymerases delta and zeta and of Rev1 in the bypass of abasic sites. Genes Dev. 2001 Apr 15;15(8):945-54. PMID:11316789 doi:10.1101/gad.882301
- ↑ Zhang H, Chatterjee A, Singh KK. Saccharomyces cerevisiae polymerase zeta functions in mitochondria. Genetics. 2006 Apr;172(4):2683-8. Epub 2006 Feb 1. PMID:16452144 doi:genetics.105.051029
- ↑ Morrison A, Christensen RB, Alley J, Beck AK, Bernstine EG, Lemontt JF, Lawrence CW. REV3, a Saccharomyces cerevisiae gene whose function is required for induced mutagenesis, is predicted to encode a nonessential DNA polymerase. J Bacteriol. 1989 Oct;171(10):5659-67. PMID:2676986 doi:10.1128/jb.171.10.5659-5667.1989
- ↑ Nelson JR, Lawrence CW, Hinkle DC. Thymine-thymine dimer bypass by yeast DNA polymerase zeta. Science. 1996 Jun 14;272(5268):1646-9. PMID:8658138 doi:10.1126/science.272.5268.1646
- ↑ Malik R, Johnson RE, Ubarretxena-Belandia I, Prakash L, Prakash S, Aggarwal AK. Cryo-EM structure of the Rev1-Polζ holocomplex reveals the mechanism of their cooperativity in translesion DNA synthesis. Nat Struct Mol Biol. 2024 Sep;31(9):1394-1403. PMID:38720088 doi:10.1038/s41594-024-01302-w
