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MOLECULAR GENETICS
Unit 2: Sex Determination and Dosage Compensation 05 hrs
Sex determination in mammals and Drosophila; Secondary sex determination in humans; Dosage
compensation in mammals and Drosophila.
Unit 3: Genetic Recombination 14 hrs
Mechanism of recombination – Holliday, White House, Messelson and Radding models; Enzymes
involved in homologous and site-specific recombination; Breakage and reunion of DNA at specific
sites; Synapsis of homologous duplexes; Role of Rec A in recombination; Genetic recombination in
Bacteria - Transformation, natural transformation systems, mechanism, gene mapping by
transformation; Conjugation – discovery, interrupted mating and temporal mapping, Hfr; Transduction
– Generalized and specialized transduction; Gene mapping by specialized transduction, abortive
transduction; Identification and selection of mutants.
Unit 4: Transposons 10 hrs
Bacterial and yeast transposons; Replicative and non-replicative transpositions; Common intermediates
for transpositions – role of transposase and resolvase; Controlling elements in Bacteria; Ac Ds system
in maize; P elements in Drosophila; Transposons in humans; Retrotransposons.
GENETIC
RECOMBINATION
Recombination is the production of new DNA molecule(s)
from two parental DNA molecules or different segments of
the same DNA molecule.
Types of recombination:
General or homologous recombination occurs between
DNA molecules of very similar sequence, such as
homologous chromosomes in diploid organisms (meiotic
recombination).
Illegitimate or nonhomologous recombination occurs in
regions where no large scale sequence similarity is
apparent,
e.g. translocations between different chromosomes or
deletions that remove several genes along a
chromosome.
• Site-specific recombination systems mediate DNA
rearrangements by breaking and joining DNA molecules at
two specific sites, termed recombination targets (RTs).
• Site-specific recombination requires a special enzymatic
machinery, basically one enzyme or enzyme system for
each particular site.
• Good examples are the systems for integration of some
bacteriophage, such as λ, into a bacterial chromosome
and the rearrangement of immunoglobulin genes in
vertebrate animals.
• Replicative recombination generates a new copy of a
segment of DNA.
• Many transposable elements use a process of replicative
recombination to generate a new copy of the transposable
element at a new location.
TYPES OF RECOMBINATION
HOMOLOGOUS
RECOMBINATION
Functions served:
Meiotic crossing over leading to reassortment
of alleles on a chromosome
DNA repair
Resuming a stalled replication fork
MODELS FOR HOMOLOGOUS RECOMBINATION
1.White House Model-1963
(Polaron-Hybrid DNA Exchange Model)
Proposed and developed by Whitehouse and Hastings
Defines a ‘polaron’ as a segment of the
Chromosome where Hybrid DNA is formed and
cross over takes place.
Steps:
Two homologous double stranded DNA align
together
An endonuclease nicks the DNA in one strand of
each DNA molecule at the start of a polaron
(depicted as solid circles in the image)
• The nicks are made in strands of opposite polarity (unlike holiday
model)
• The nicked strands starts unwinding from their sister strands.
• New DNA strands are synthesized along the single stranded regions
using the intact strand as the template.
• The newly synthesized DNA separatesform their templates
• The newly synthesized strands base pair with their non-sister strands
and form double stranded regions
• The intact strands which are single stranded are degraded and the
remaining nicks are sealed. This completes recombination.
• The mismatches in the DNA hybrids may be repaired later to give non-
reciprocal recombination (due to gene conversion)
• If it is not repaired it can lead to post meiotic segregation
Recombination Models.pdf
2. HOLLIDAY MODEL (1964)
This model was proposed by Robin Holliday
The model illustrates the strand invasion, branch migration
and junction resolution in a simple and effective way.
Explained reciprocal exchange of DNA segments, gene
conversion and post meiotic segregation
But this model is insufficient to explain the mechanism of
crossing over because
It involves only single stranded breaks (Meiotic
recombination is initiated by Double stranded breaks)
No DNA synthesis takesplace
(all recombination events involve some new DNA synthesis)
STEPS
1. Alignment of two homologous DNA molecules
2. Introduction of breaks in both strands of DNA
3. Strand Invasion: Formation of initial short regions of
base pairing between two recombining DNA
molecules
Occurs when a single stranded region from one
parent DNA pairs with a strand of the other homolog
Strand invasion results in the connection
between two DNA molecules by crossing DNA
strands. This structure is called Holliday
Junction
Branchmigration: the holliday junction moves
along the DNA by repeated melting and formation
of base pairs.
Resolution: this involves the cleavage of the holliday
junction.
This steps finishes the process of genetic exchange
depending on the type of resolution both cross over
DNA and non cross over DNA can be produced
Recombination Models.pdf
Recombination Models.pdf
Recombination Models.pdf
Recombination Models.pdf
3. MESELSON-RADDING MODEL
(1975)
The model proposed by Meselson and Radding generates the
Holliday structure with one single-strand cut in only one
chromosome in contrast with the Holliday model, in which a
nick is made in one strand in each of the two homologous
chromatids.
Steps involved
(a) A duplex is cut on one chain.
(b) DNA polymerase displaces one chain.
(c) The resulting single chain displaces its counterpart in the
homolog.
(d) This displaced chain is enzymatically digested.
(e) Ligation completes the formation of a Holliday junction,
which is genetically asymmetric in that only one of the two
duplexes has a region of potentially heteroduplex DNA. If the
junction migrates, heteroduplex DNA can arise on both
duplexes.
(f) Resolution of the junction occurs as in the Holliday model.
Recombination Models.pdf
4.DOUBLE STRAND BREAK REPAIR PATHWAY
FOR HOMOLOGOUS RECOMBINATION (1983)
Involves double stranded DNA breaks instead of single stranded
breaks.
The break is introduced only in one DNA duplex involved in
recombination
The DNA adjacent to the break site is then degraded to produce
single stranded tails with a free 3’ end.
One of the ssDNA tails then invade the other duplex.
The strand displaced from the second duplex invades the first duplex.
New DNA synthesis takes place at the 3’ ends of the invading strand
and the non-invading broken strand.
The process of branch migration results in formation of two Holliday
junctions which can be resolved in many alternative forms
Based on the type of resolution either a splice/cross-over
product or a patch/non cross over product is obtained
Recombination Models.pdf
Recombination Models.pdf
RESOLUTION OF DOUBLE–
HOLLIDAY JUNCTION
ENZYMES INVOLVED IN HOMOLOGOUS
RECOMBINATION IN E. COLI
Protein Function
RecBCD Processes DNA togenerate single
stranded regions
RecA Brings about strandexchange
Ruv A, RuvB Enables branch migration
Ruv C Holliday Junctionresolution
In addition to these dedicated proteins involved in
recombination DNA polymerases, Single stranded DNA binding
proteins, topoisomerases and ligases also take part in the process
In bacteria there is no enzyme known to introduce breaks in
DNA.
Breaks arise by UV rays, or by replication errors
RECBCD
Processes broken DNA molecules to generate regions of ssDNA.
Helps load the recA strand exchange protein to the ssDNA ends.
Helps a cell to choose whether to recombine with or destroy
DNA molecules that enter the cell
It contains three subunits, the B, C & D subunits. (total size-330
KDa)
Ithas both helicase ( B& D subunits) and nuclease activities
Itreleases energy by hydrolysis of ATP to fuel its activities
The activity of the enzyme complex is under the control of
Chi (crossover hotspot instigator)
Chi sites are regions in the bacterial genome near to which
recombination occurs at a higher frequency than expected
RECA
Rec A is the most important protein in homologous recombination
Itbelongs to a family of proteins called strand –exchange proteins
These proteins catalyse the pairing of homologous DNA molecules by
Search for sequence matches between strands of DNA
Generate regions of complementary base pairing between the
DNA
In order to perform its function, multiple (many to hundreds)
subunits of RecA protein bind to single stranded DNA with 3’
overhangs to produce a protein-DNAfilament.
The protein DNA filament is extended in length with a distance of
around 5 A between bases as against the normal 3.4 A
The RecA filament has a primary binding site that is bound to the
single stranded DNA and a secondary binding site that can
accommodate double stranded DNA
Homologs of RecA are found in Archae (Rad A) & Eukaryotes (Rad
51, Dmc1)
STAGES OF RECA CATALYSED
STRAND EXCHANEGE
1. RecA assembles on one of the participating DNA
molecule containing a region of ssDNA to form a recA-ss
DNA complex that searches for regions of
complimentarity in the other strand.
The secondary binding site samples large stretches
of DNA for sequence complimentarity
A sequence homology of around 15 bp triggers strand
exchange
STAGES OF REC A CATALYZED
STRAND EXCHANGE
2. Once a region of base pair complementarity is located
Rec A promotes the formation of a stable three
stranded complex called Joint molecule.
3. Then the single stranded DNA in the primary site binds
to its compliment in the duplex bound by the
secondary site.
This process of strand exchange involves breakage and
formation of bonds
RUV AB
Ruv A protein (a tetramer) recognises and binds
specifically to Hollidayjunctions
Itrecruits Ruv B protein to the site.
Ruv B is a hexameric protein which acts as a
ATPase
The energy derived by hydrolysis of ATP by RuvB
enables the exchange of base pairs that result in
branch migration
RUVAB IN A HOLLIDAY
JUNCTION
RUV C
Ruv C is the major endonuclease that resoves holliday
junction in bacteria
Itfunctions in concert withRuvAB
RuvC is recognises the junction in complex with RuvAB
and nicks two DNA strands of the same polarity
Depending on the strands which are cut either patch
products or splice products are formed
The protein exhibits some level of sepecificity
It recognises the sequence 5”-A/T-T-T-T -G/C-3” which is
on an average present once every 64 nucleotides in the
genome
This specificity ensures that at least some branch
migration has happened before the resolution of the
junction
RUV C IN A HOLLIDAY
JUNCTION
ENZYMES INVOLVED IN EUKARYOTIC
RECOMBINATION (MEIOTIC RECOMBINATION)
Homologous recombination events that occur during
meiosis are called meiotic recombination.
Many proteins associate together to form large
recombination factories to bring about the process
Few well characterised enzymes are listed below
SPO11
• SPO11 gene encodes a protein that introduces DSBs in
chromosomal DNA to initiate meiotic recombination.
• The Spo11 protein cuts the DNA at many chromosomal locations,
with little sequence selectivity, but at a very specific time during
meiosis.
• Spo11- mediated DNA cleavage occurs right around the time
when the replicated homologous chromosomes start to pair.
• Spo11 cut sites, although frequent, are not randomly distributed
along the DNA.
• The mechanism of Spo11 DNA cleavage is as follows:
• A specific tyrosine side chain in the Spo11 protein attacks the
phosphodiester backbone to cut the DNA and generate a covalent
complex between the protein and the severed DNA strand.
• Two subunits of Spo11 cleave the DNA two nucleotides apart on
the two DNA strands to make a staggered DSB.
• Spo11 shares this DNA cleavage mechanism with the DNA
topoisomerases and the site-specific recombinases.
SPO 11MECHANISM
MRX–ENZYME COMPLEX
• During meiotic recombination, the MRX–enzyme complex is
responsible for this DNA-processing event.
• MRX is composed of protein subunits called Mre11, Rad50,
and Xrs2; the first letters of these subunits give the complex
its name.
• Processing of the DNA at the break site occurs exclusively
on the DNA strand that terminates with a 50 end—that is,
the strands covalently attached to the Spo11 protein (as
described above).
• The strands terminating with 3’ends are not degraded.
• This DNA-processing reaction is therefore called 5’-to-3’
resection.
• The MRX-dependent 5’-to-3’ resection generates the long
ssDNA tails with 30 ends that are often 1 kb or longer.
• The MRX complex is also thought to remove the DNA-linked
Spo11.
RAD51 AND DMC1
• Eukaryotes encode two well-characterized homologs
of the bacterial RecA protein: Rad51 and Dmc1.
• Both proteins function in meiotic recombination.
• Whereas Rad51 is widely expressed in cells dividing
mitotically and meiotically, Dmc1 is expressed only as
cells enter meiosis.
• Dmc1- dependent recombination is preferentially
between the non-sister homologous chromatids,
rather than between the sisters.
• They promote strand invasion & exchange between
non sister chromatids
• Rad 51 associate with single stranded DNA to form
DNA-protein filaments
• The assembly of these filaments are promoted by
another protein called Rad52
RAD52
• Rad52 is another essential recombination protein
that interacts with Rad51.
• Rad52 functions to promote assembly of Rad51
DNA filaments, the active form of Rad51.
• It does this by antagonizing the action of RPA, the
major ssDNA-binding protein present in eukaryotic
cells.
• In this respect, Rad52 shares an activity with the E.
coli RecBCD protein.
• Rad52 protein also promotes the annealing and
base pairing of complementary ssDNA molecules,
and this activity may also play a role in the strand-
pairing reactions that occur during initiation
of recombination
MUS 81
Essential formeiosis
Isan endonuclease
Probably involved in holiday junction
resolution
ENZYME
MEDIATED
RECOMBINATION
IN
EUKARYOTES

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Recombination Models.pdf

  • 1. MOLECULAR GENETICS Unit 2: Sex Determination and Dosage Compensation 05 hrs Sex determination in mammals and Drosophila; Secondary sex determination in humans; Dosage compensation in mammals and Drosophila. Unit 3: Genetic Recombination 14 hrs Mechanism of recombination – Holliday, White House, Messelson and Radding models; Enzymes involved in homologous and site-specific recombination; Breakage and reunion of DNA at specific sites; Synapsis of homologous duplexes; Role of Rec A in recombination; Genetic recombination in Bacteria - Transformation, natural transformation systems, mechanism, gene mapping by transformation; Conjugation – discovery, interrupted mating and temporal mapping, Hfr; Transduction – Generalized and specialized transduction; Gene mapping by specialized transduction, abortive transduction; Identification and selection of mutants. Unit 4: Transposons 10 hrs Bacterial and yeast transposons; Replicative and non-replicative transpositions; Common intermediates for transpositions – role of transposase and resolvase; Controlling elements in Bacteria; Ac Ds system in maize; P elements in Drosophila; Transposons in humans; Retrotransposons.
  • 3. Recombination is the production of new DNA molecule(s) from two parental DNA molecules or different segments of the same DNA molecule. Types of recombination: General or homologous recombination occurs between DNA molecules of very similar sequence, such as homologous chromosomes in diploid organisms (meiotic recombination). Illegitimate or nonhomologous recombination occurs in regions where no large scale sequence similarity is apparent, e.g. translocations between different chromosomes or deletions that remove several genes along a chromosome.
  • 4. • Site-specific recombination systems mediate DNA rearrangements by breaking and joining DNA molecules at two specific sites, termed recombination targets (RTs). • Site-specific recombination requires a special enzymatic machinery, basically one enzyme or enzyme system for each particular site. • Good examples are the systems for integration of some bacteriophage, such as λ, into a bacterial chromosome and the rearrangement of immunoglobulin genes in vertebrate animals. • Replicative recombination generates a new copy of a segment of DNA. • Many transposable elements use a process of replicative recombination to generate a new copy of the transposable element at a new location.
  • 6. HOMOLOGOUS RECOMBINATION Functions served: Meiotic crossing over leading to reassortment of alleles on a chromosome DNA repair Resuming a stalled replication fork
  • 7. MODELS FOR HOMOLOGOUS RECOMBINATION 1.White House Model-1963 (Polaron-Hybrid DNA Exchange Model) Proposed and developed by Whitehouse and Hastings Defines a ‘polaron’ as a segment of the Chromosome where Hybrid DNA is formed and cross over takes place. Steps: Two homologous double stranded DNA align together An endonuclease nicks the DNA in one strand of each DNA molecule at the start of a polaron (depicted as solid circles in the image)
  • 8. • The nicks are made in strands of opposite polarity (unlike holiday model) • The nicked strands starts unwinding from their sister strands. • New DNA strands are synthesized along the single stranded regions using the intact strand as the template. • The newly synthesized DNA separatesform their templates • The newly synthesized strands base pair with their non-sister strands and form double stranded regions • The intact strands which are single stranded are degraded and the remaining nicks are sealed. This completes recombination. • The mismatches in the DNA hybrids may be repaired later to give non- reciprocal recombination (due to gene conversion) • If it is not repaired it can lead to post meiotic segregation
  • 10. 2. HOLLIDAY MODEL (1964) This model was proposed by Robin Holliday The model illustrates the strand invasion, branch migration and junction resolution in a simple and effective way. Explained reciprocal exchange of DNA segments, gene conversion and post meiotic segregation But this model is insufficient to explain the mechanism of crossing over because It involves only single stranded breaks (Meiotic recombination is initiated by Double stranded breaks) No DNA synthesis takesplace (all recombination events involve some new DNA synthesis)
  • 11. STEPS 1. Alignment of two homologous DNA molecules 2. Introduction of breaks in both strands of DNA 3. Strand Invasion: Formation of initial short regions of base pairing between two recombining DNA molecules Occurs when a single stranded region from one parent DNA pairs with a strand of the other homolog Strand invasion results in the connection between two DNA molecules by crossing DNA strands. This structure is called Holliday Junction
  • 12. Branchmigration: the holliday junction moves along the DNA by repeated melting and formation of base pairs. Resolution: this involves the cleavage of the holliday junction. This steps finishes the process of genetic exchange depending on the type of resolution both cross over DNA and non cross over DNA can be produced
  • 17. 3. MESELSON-RADDING MODEL (1975) The model proposed by Meselson and Radding generates the Holliday structure with one single-strand cut in only one chromosome in contrast with the Holliday model, in which a nick is made in one strand in each of the two homologous chromatids. Steps involved (a) A duplex is cut on one chain. (b) DNA polymerase displaces one chain. (c) The resulting single chain displaces its counterpart in the homolog. (d) This displaced chain is enzymatically digested. (e) Ligation completes the formation of a Holliday junction, which is genetically asymmetric in that only one of the two duplexes has a region of potentially heteroduplex DNA. If the junction migrates, heteroduplex DNA can arise on both duplexes. (f) Resolution of the junction occurs as in the Holliday model.
  • 19. 4.DOUBLE STRAND BREAK REPAIR PATHWAY FOR HOMOLOGOUS RECOMBINATION (1983) Involves double stranded DNA breaks instead of single stranded breaks. The break is introduced only in one DNA duplex involved in recombination The DNA adjacent to the break site is then degraded to produce single stranded tails with a free 3’ end. One of the ssDNA tails then invade the other duplex. The strand displaced from the second duplex invades the first duplex. New DNA synthesis takes place at the 3’ ends of the invading strand and the non-invading broken strand. The process of branch migration results in formation of two Holliday junctions which can be resolved in many alternative forms Based on the type of resolution either a splice/cross-over product or a patch/non cross over product is obtained
  • 23. ENZYMES INVOLVED IN HOMOLOGOUS RECOMBINATION IN E. COLI Protein Function RecBCD Processes DNA togenerate single stranded regions RecA Brings about strandexchange Ruv A, RuvB Enables branch migration Ruv C Holliday Junctionresolution In addition to these dedicated proteins involved in recombination DNA polymerases, Single stranded DNA binding proteins, topoisomerases and ligases also take part in the process In bacteria there is no enzyme known to introduce breaks in DNA. Breaks arise by UV rays, or by replication errors
  • 24. RECBCD Processes broken DNA molecules to generate regions of ssDNA. Helps load the recA strand exchange protein to the ssDNA ends. Helps a cell to choose whether to recombine with or destroy DNA molecules that enter the cell It contains three subunits, the B, C & D subunits. (total size-330 KDa) Ithas both helicase ( B& D subunits) and nuclease activities Itreleases energy by hydrolysis of ATP to fuel its activities The activity of the enzyme complex is under the control of Chi (crossover hotspot instigator) Chi sites are regions in the bacterial genome near to which recombination occurs at a higher frequency than expected
  • 25. RECA Rec A is the most important protein in homologous recombination Itbelongs to a family of proteins called strand –exchange proteins These proteins catalyse the pairing of homologous DNA molecules by Search for sequence matches between strands of DNA Generate regions of complementary base pairing between the DNA In order to perform its function, multiple (many to hundreds) subunits of RecA protein bind to single stranded DNA with 3’ overhangs to produce a protein-DNAfilament. The protein DNA filament is extended in length with a distance of around 5 A between bases as against the normal 3.4 A The RecA filament has a primary binding site that is bound to the single stranded DNA and a secondary binding site that can accommodate double stranded DNA Homologs of RecA are found in Archae (Rad A) & Eukaryotes (Rad 51, Dmc1)
  • 26. STAGES OF RECA CATALYSED STRAND EXCHANEGE 1. RecA assembles on one of the participating DNA molecule containing a region of ssDNA to form a recA-ss DNA complex that searches for regions of complimentarity in the other strand. The secondary binding site samples large stretches of DNA for sequence complimentarity A sequence homology of around 15 bp triggers strand exchange
  • 27. STAGES OF REC A CATALYZED STRAND EXCHANGE 2. Once a region of base pair complementarity is located Rec A promotes the formation of a stable three stranded complex called Joint molecule. 3. Then the single stranded DNA in the primary site binds to its compliment in the duplex bound by the secondary site. This process of strand exchange involves breakage and formation of bonds
  • 28. RUV AB Ruv A protein (a tetramer) recognises and binds specifically to Hollidayjunctions Itrecruits Ruv B protein to the site. Ruv B is a hexameric protein which acts as a ATPase The energy derived by hydrolysis of ATP by RuvB enables the exchange of base pairs that result in branch migration
  • 29. RUVAB IN A HOLLIDAY JUNCTION
  • 30. RUV C Ruv C is the major endonuclease that resoves holliday junction in bacteria Itfunctions in concert withRuvAB RuvC is recognises the junction in complex with RuvAB and nicks two DNA strands of the same polarity Depending on the strands which are cut either patch products or splice products are formed The protein exhibits some level of sepecificity It recognises the sequence 5”-A/T-T-T-T -G/C-3” which is on an average present once every 64 nucleotides in the genome This specificity ensures that at least some branch migration has happened before the resolution of the junction
  • 31. RUV C IN A HOLLIDAY JUNCTION
  • 32. ENZYMES INVOLVED IN EUKARYOTIC RECOMBINATION (MEIOTIC RECOMBINATION) Homologous recombination events that occur during meiosis are called meiotic recombination. Many proteins associate together to form large recombination factories to bring about the process Few well characterised enzymes are listed below
  • 33. SPO11 • SPO11 gene encodes a protein that introduces DSBs in chromosomal DNA to initiate meiotic recombination. • The Spo11 protein cuts the DNA at many chromosomal locations, with little sequence selectivity, but at a very specific time during meiosis. • Spo11- mediated DNA cleavage occurs right around the time when the replicated homologous chromosomes start to pair. • Spo11 cut sites, although frequent, are not randomly distributed along the DNA. • The mechanism of Spo11 DNA cleavage is as follows: • A specific tyrosine side chain in the Spo11 protein attacks the phosphodiester backbone to cut the DNA and generate a covalent complex between the protein and the severed DNA strand. • Two subunits of Spo11 cleave the DNA two nucleotides apart on the two DNA strands to make a staggered DSB. • Spo11 shares this DNA cleavage mechanism with the DNA topoisomerases and the site-specific recombinases.
  • 35. MRX–ENZYME COMPLEX • During meiotic recombination, the MRX–enzyme complex is responsible for this DNA-processing event. • MRX is composed of protein subunits called Mre11, Rad50, and Xrs2; the first letters of these subunits give the complex its name. • Processing of the DNA at the break site occurs exclusively on the DNA strand that terminates with a 50 end—that is, the strands covalently attached to the Spo11 protein (as described above). • The strands terminating with 3’ends are not degraded. • This DNA-processing reaction is therefore called 5’-to-3’ resection. • The MRX-dependent 5’-to-3’ resection generates the long ssDNA tails with 30 ends that are often 1 kb or longer. • The MRX complex is also thought to remove the DNA-linked Spo11.
  • 36. RAD51 AND DMC1 • Eukaryotes encode two well-characterized homologs of the bacterial RecA protein: Rad51 and Dmc1. • Both proteins function in meiotic recombination. • Whereas Rad51 is widely expressed in cells dividing mitotically and meiotically, Dmc1 is expressed only as cells enter meiosis. • Dmc1- dependent recombination is preferentially between the non-sister homologous chromatids, rather than between the sisters. • They promote strand invasion & exchange between non sister chromatids • Rad 51 associate with single stranded DNA to form DNA-protein filaments • The assembly of these filaments are promoted by another protein called Rad52
  • 37. RAD52 • Rad52 is another essential recombination protein that interacts with Rad51. • Rad52 functions to promote assembly of Rad51 DNA filaments, the active form of Rad51. • It does this by antagonizing the action of RPA, the major ssDNA-binding protein present in eukaryotic cells. • In this respect, Rad52 shares an activity with the E. coli RecBCD protein. • Rad52 protein also promotes the annealing and base pairing of complementary ssDNA molecules, and this activity may also play a role in the strand- pairing reactions that occur during initiation of recombination
  • 38. MUS 81 Essential formeiosis Isan endonuclease Probably involved in holiday junction resolution