TY - JOUR
T1 - Regulation of mitotic recombination between DNA repeats in centromeres
AU - Zafar, Faria
AU - Okita, Akiko K.
AU - Onaka, Atsushi T.
AU - Su, Jie
AU - Katahira, Yasuhiro
AU - Nakayama, Jun Ichi
AU - Takahashi, Tatsuro S.
AU - Masukata, Hisao
AU - Nakagawa, Takuro
N1 - Funding Information:
JSPS KAKENHI [JP21114513, JP23570212, JP26114711 to T.N.; JP23114005, JP26291072, JP16H01315 to J.N.]; Ninety-Nine Asia Student Scholarship Foundation Fellowship (to F.Z.); Japan Student Service Organization Fellowship (JASSO) (to F.Z.). Funding for open access charge: JSPS KAKENHI [JP21114513, JP23570212, JP26114711 to T.N.]. Conflict of interest statement. None declared.
Publisher Copyright:
© The Author(s) 2017.
PY - 2017/11/2
Y1 - 2017/11/2
N2 - Centromeres that are essential for faithful segregation of chromosomes consist of unique DNA repeats in many eukaryotes. Although recombination is under-represented around centromeres during meiosis, little is known about recombination between centromere repeats in mitotic cells. Here, we compared spontaneous recombination that occurs between ade6B/ade6X inverted repeats integrated at centromere 1 (cen1) or at a non-centromeric ura4 locus in fission yeast. Remarkably, distinct mechanisms of homologous recombination (HR) were observed in centromere and non-centromere regions. Rad51-dependent HR that requires Rad51, Rad54 and Rad52 was predominant in the centromere, whereas Rad51-independent HR that requires Rad52 also occurred in the arm region. Crossovers between inverted repeats (i.e. inversions) were underrepresented in the centromere as compared to the arm region. While heterochromatin was dispensable, Mhf1/CENP-S, Mhf2/CENP-X histone-fold proteins and Fml1/FANCM helicase were required to suppress crossovers. Furthermore, Mhf1 and Fml1 were found to prevent gross chromosomal rearrangements mediated by centromere repeats. These data uncovered the regulation of mitotic recombination between DNA repeats in centromeres and its physiological role in maintaining genome integrity.
AB - Centromeres that are essential for faithful segregation of chromosomes consist of unique DNA repeats in many eukaryotes. Although recombination is under-represented around centromeres during meiosis, little is known about recombination between centromere repeats in mitotic cells. Here, we compared spontaneous recombination that occurs between ade6B/ade6X inverted repeats integrated at centromere 1 (cen1) or at a non-centromeric ura4 locus in fission yeast. Remarkably, distinct mechanisms of homologous recombination (HR) were observed in centromere and non-centromere regions. Rad51-dependent HR that requires Rad51, Rad54 and Rad52 was predominant in the centromere, whereas Rad51-independent HR that requires Rad52 also occurred in the arm region. Crossovers between inverted repeats (i.e. inversions) were underrepresented in the centromere as compared to the arm region. While heterochromatin was dispensable, Mhf1/CENP-S, Mhf2/CENP-X histone-fold proteins and Fml1/FANCM helicase were required to suppress crossovers. Furthermore, Mhf1 and Fml1 were found to prevent gross chromosomal rearrangements mediated by centromere repeats. These data uncovered the regulation of mitotic recombination between DNA repeats in centromeres and its physiological role in maintaining genome integrity.
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U2 - 10.1093/nar/gkx763
DO - 10.1093/nar/gkx763
M3 - Article
C2 - 28977643
AN - SCOPUS:85037976040
SN - 0305-1048
VL - 45
SP - 11222
EP - 11235
JO - Nucleic acids research
JF - Nucleic acids research
IS - 19
ER -