@article {133,
	title = {DNA REPAIR. Mus81 and converging forks limit the mutagenicity of replication fork breakage.},
	journal = {Science},
	volume = {349},
	year = {2015},
	month = {2015 Aug 14},
	pages = {742-7},
	abstract = {<p>Most spontaneous DNA double-strand breaks (DSBs) result from replication-fork breakage. Break-induced replication (BIR), a genome rearrangement-prone repair mechanism that requires the Pol32/POLD3 subunit of eukaryotic DNA Polδ, was proposed to repair broken forks, but how genome destabilization is avoided was unknown. We show that broken fork repair initially uses error-prone Pol32-dependent synthesis, but that mutagenic synthesis is limited to within a few kilobases from the break by Mus81 endonuclease and a converging fork. Mus81 suppresses template switches between both homologous sequences and diverged human Alu repetitive elements, highlighting its importance for stability of highly repetitive genomes. We propose that lack of a timely converging fork or Mus81 may propel genome instability observed in cancer. </p>},
	keywords = {Alu Elements, Base Sequence, DNA Breaks, Double-Stranded, DNA Repair, DNA Replication, DNA-Binding Proteins, DNA-Directed DNA Polymerase, Endonucleases, Genomic Instability, Humans, Molecular Sequence Data, Neoplasms, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins},
	issn = {1095-9203},
	doi = {10.1126/science.aaa8391},
	author = {Mayle, Ryan and Campbell, Ian M and Beck, Christine R and Yu, Yang and Wilson, Marenda and Shaw, Chad A and Bjergbaek, Lotte and Lupski, James R and Ira, Grzegorz}
}
@article {202,
	title = {Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas.},
	journal = {Int J Cancer},
	volume = {137},
	year = {2015},
	month = {2015 Jul 15},
	pages = {320-31},
	abstract = {<p>In a number of families with colorectal adenomatous polyposis or suspected Lynch syndrome/HNPCC, no germline alteration in the APC, MUTYH, or mismatch repair (MMR) genes are found. Missense mutations in the polymerase genes POLE and POLD1 have recently been identified as rare cause of multiple colorectal adenomas and carcinomas, a condition termed polymerase proofreading-associated polyposis (PPAP). The aim of the present study was to evaluate the clinical relevance and phenotypic spectrum of polymerase germline mutations. Therefore, targeted sequencing of the polymerase genes POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3 and POLE4 was performed in 266 unrelated patients with polyposis or fulfilled Amsterdam criteria. The POLE mutation c.1270C>G;p.Leu424Val was detected in four unrelated patients. The mutation was present in 1.5\% (4/266) of all patients, 4\% (3/77) of all familial cases and 7\% (2/30) of familial polyposis cases. The colorectal phenotype in 14 affected individuals ranged from typical adenomatous polyposis to a HNPCC phenotype, with high intrafamilial variability. Multiple colorectal carcinomas and duodenal adenomas were common, and one case of duodenal carcinoma was reported. Additionally, various extraintestinal lesions were evident. Nine further putative pathogenic variants were identified. The most promising was c.1306C>T;p.Pro436Ser in POLE. In conclusion, a PPAP was identified in a substantial number of polyposis and familial colorectal cancer patients. Screening for polymerase proofreading mutations should therefore be considered, particularly in unexplained familial cases. The present study broadens the phenotypic spectrum of PPAP to duodenal adenomas and carcinomas, and identified novel, potentially pathogenic variants in four polymerase genes. </p>},
	keywords = {Adenoma, Adolescent, Adult, Aged, Aged, 80 and over, Child, Colorectal Neoplasms, DNA Polymerase II, DNA-Directed DNA Polymerase, Family Health, Female, Gene Frequency, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Isoenzymes, Male, Middle Aged, Mutation, Missense, Pedigree, Phenotype, Phospholipase D, Poly-ADP-Ribose Binding Proteins, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Young Adult},
	issn = {1097-0215},
	doi = {10.1002/ijc.29396},
	author = {Spier, Isabel and Holzapfel, Stefanie and Altm{\"u}ller, Janine and Zhao, Bixiao and Horpaopan, Sukanya and Vogt, Stefanie and Chen, Sophia and Morak, Monika and Raeder, Susanne and Kayser, Katrin and Stienen, Dietlinde and Adam, Ronja and N{\"u}rnberg, Peter and Plotz, Guido and Holinski-Feder, Elke and Lifton, Richard P and Thiele, Holger and Hoffmann, Per and Steinke, Verena and Aretz, Stefan}
}
